CN1124348C - 多功能性造血受体激动剂 - Google Patents
多功能性造血受体激动剂 Download PDFInfo
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Abstract
公开的内容是新型的多功能性造血受体激动剂蛋白,编码多功能性造血受体激动剂蛋白的DNA,制备多功能性造血受体激动剂蛋白的方法和使用多功能性造血受体激动剂蛋白的方法。
Description
根据35USC§119(e),本申请要求1995年10月5日提交的美国临时申请60/004,834的优先权。
发明领域
本发明描述多功能性造血受体激动剂。
发明背景
刺激骨髓细胞分化和/或增殖的集落刺激因子(CSFs)引起广泛的兴趣,是因为它们能恢复来自造血干细胞的细胞抑制水平的治疗潜力。根据它们的活性,已鉴定和区别出了在人和鼠系统中的CSF。例如,粒细胞-CSF(G-CSF)和巨噬细胞(M-CSF)体外分别刺激形成嗜中性细胞和巨噬细胞集落,而GM-CSF和白介素-3(IL-3)有更广泛的活性,刺激巨噬细胞、嗜中性和嗜酸性粒细胞集落的形成。IL-3也刺激肥大细胞、巨核细胞和纯的及混合的红细胞样集落的形成。
U.S.4,887,729和U.S.4,959,455公开了人IL-3和长臂猿IL-3的cDNA及由它们编码的蛋白序列。在蛋白序列第8位,公开序列的hIL-3是丝氨酸而不是脯氨酸。
国际专利申请(PCT)WO 88/00598号公开了长臂猿样和人样的IL-3。hIL-3含Ser8→Pro8的取代。暗示可进行由丝氨酸取代半胱氨酸,因而断裂二硫键,和在糖基化位点取代一个或多个氨基酸。
U.S.4,810,643号公开了编码人G-CSF的DNA序列。
WO 91/02754号公开了一种包括GM-CSF和IL-3的融合蛋白,与单独的GM-CSF或IL-3相比,该蛋白增加了生物活性。还公开了作为多功能性造血受体激动剂组分的非糖基化的IL-3和GM-CSF类似物蛋白。
WO 92/04455号公开了由IL-3和一种来自IL-3、IL-6、IL-7、IL-9、IL-11、EPO和G-CSF的淋巴因子融合而成的融合蛋白。
WO 95/21197和WO 95/21254号公开了具有广泛的多功能造血特性的融合蛋白。
GB 2,285,446号专利叙述了c-mpl配体(血小板生成素)和各种形式的血小板生成素,已表明它们影响巨核细胞和巨核细胞祖细胞的增殖、分化和成熟,可用于治疗血小板减少症。
EP 675,201 A1号专利叙述了c-mpl配体(巨核细胞生长和发育因子(MGDF)),c-mpl配体的等位基因变异以及附着于如聚乙二醇的水溶性聚合物上的c-mpl配体。
WO 95/21920号提供了鼠和人c-mpl配体和其多肽片段。这些蛋白用于体内和离体治疗,以刺激产生血小板。
蛋白序列的重排
在进化过程中,DNA序列的重排在产生蛋白结构和功能多样性中起重要的作用。基因重复和外显子穿梭提供了一种快速产生多样性的重要机制,因而使生物具有竞争优势,尤其是由于基本突变率低时(Doolittle,蛋白质科学1:191-200,1992)。
重组DNA方法的发展使研究序列移位对蛋白折叠、结构和功能的影响成为可能。用于产生新序列的方法与天然产生的蛋白对相似,蛋白对由于其氨基酸序列的线性改组而相关(Cunningham等,美国国家科学院院报76:3218-3222,1979;Teather & Erfle,细菌学杂志172:3837-3841,1990;Schimming等,欧洲生物化学杂志204:13-19,1992;Yamiuchi和Minamikawa,FEBS Lett.260:127-130,1991;MacGregor等,FEBS Lett.378:263-266)。这种对蛋白重排类型的首先体外应用由Goldenberg和Creighton加以描述(分子生物学杂志165:407-413,1983)。新N-末端选在原始序列的一个内部位点(断裂点)上,新序列与原始序列自断裂点直到位于原始C-末端或附近的一个氨基酸的氨基酸顺序相同。在这点上新序列直接或通过序列的附加部分(连接序列),与位于原始序列N-末端或其附近的一个氨基酸相连,然后新序列续以与原始相同的序列,一直到在相对于原始序列的断裂位点为N-末端的氨基酸或其附近的一点上,该残基形成链的新的C-末端。
这种方法已被应用到58-462个氨基酸大小的蛋白上(Goldenberg& Creighton,分子生物学杂志165:407-413,1983;Li & Coffinno,分子细胞生物学13:2377-2383,1993)。所检查的蛋白代表广泛的结构种类,包括含占优势的α-螺旋(白介素-4;Kreitman等,细胞因子7:311-318,1995),β-片层(白介素-1;Horlick等,蛋白质工程5:427-431,1992),或者两者的混和体(酵母磷酸核糖基邻氨基苯甲酸异构酶;Luger等,科学243:206-210,1989)。蛋白功能的主要种类表现在这些序列重组研究之中:
酶
T4溶菌酶 Zhang等,生物化学32:12311-12318,
1993;Zhang等,天然结构生物学1:434
-438(1995)
二氢叶酸还原酶 Buchwalder等,生物化学31:1621-
1630,1994;Protasova等,蛋白质工程
7:1373-1377,1995)
核酸酶T1 Mullins等,美国化学协会杂志116:5529
-5533,1994;Garrett等,蛋白质科学
5:204-211,1996)
芽孢杆菌β葡聚糖酶 Hahn等,美国国家科学院院报91:10417
-10421,1994)
天冬氨酸转氨甲酰酶 Yang & Schachman,美国国家科学院院报
90:11980-11984,1993)
磷酸核糖基邻氨基 Luger等,科学243:206-210,1989;
苯甲酸异构酶 (Luger等,蛋白质工程3:249-258,
1990)
胃蛋白酶/胃蛋白酶 Lin等,蛋白质化学4:159-166,1995)
酶原
磷酸甘油醛-3- Vignais等,蛋白质科学4:994-1000,
磷酸脱氢酶 1995)
鸟氨酸脱羧酶 Li & Coffino,分子细胞生物学13:2377
-2383,1993)
酵母磷酸甘油酸 Ritco-Vonsovici等,生物化学34:16543
脱氢酶 -16551,1995)
酶抑制剂
碱性胰蛋白酶抑制剂 Goldenberg & Creighton,分子生物学杂志
165:407-413,1983)
细胞因子类
白介素-1β Horlick等,蛋白质工程5:427-431,
1992)
白介素-4 Kreitman等,细胞因子7:311-318,
1995)
酪氨酸激酶识别结构域
α-血影蛋白SH3 Viguera等,分子生物学杂志247:670
结构域 -681,1995)
跨膜蛋白
Omp A Koebnik & Krmer,分子生物学杂志
250:617-626,1995)
嵌合蛋白
白介素-4-假单胞菌 Kreitman等,美国国家科学院院报91:
外毒素 6889-6893,1994)
这些研究结果非常易变。在许多情况下,观察到很低的活性、可溶性或热动力学稳定性(大肠杆菌二氢叶酸还原酶、天冬氨酸转氨甲酰酶、磷酸核糖基邻氨基苯甲酸异构酶、甘油醛-3-磷酸脱氢酶、鸟氨酸脱羧酶、Omp A、酵母磷酸甘油酸脱氢酶)。在其他情况下,序列重排蛋白出现许多与其天然相似物几乎相同的特性(碱性胰蛋白酶抑制剂、T4溶菌酶、核酸酶T1、芽孢杆菌β-葡聚糖酶、白介素-1β、α-血影蛋白SH3结构域、胃蛋白酶原、白介素-4)。在例外的情况下,观察到对天然序列的某些特性未曾预料到的改进,如可溶性和对重排的α-血影蛋白SH3结构域序列的重新折叠率,变换的白介素-4-假单胞菌外毒素融合分子的受体亲和性和抗肿瘤活性(Kreitman等,美国国家科学院院报91:6889-6893,1994;Kreitman等,癌症研究55:3357-3363,1995)。
对研究的这些类型的原初目的是研究短距离和长距离相互作用在蛋白折叠和稳定性中的作用。这种类型的序列重排把在原始序列中长距离相互作用的亚基变换成新序列中的短距离相互作用,反之亦然。许多这些序列的重排能获得至少具有某些活性的构象的事实,是蛋白质折叠由多种折叠途径发生的有说服力的证据。(Viguera等,分子生物学杂志247:670-681,1995)。在α-血影蛋白SH3结构域的情况中,选择新末端的部位与β-受体激动剂相对应。本发明也叙述了含多功能性造血受体激动剂的药用组合物,和应用多功能性造血受体激动剂的方法。
除了本发明体内应用多功能性造血受体激动剂外,还展望了体外应用包括在输注到病人体内之前刺激骨髓和血细胞活化和生长的能力。
本发明的多功能性受体激动剂也能用下列通式表示:
(T1)a-(L1)b-X1-(L)c-X2-(L2)d-(T2)e
X1-(L)c-X2-(L)-Y1-(L)c-Y2
其中:
X1是包含对应于原始蛋白n+1到J残基的氨基酸序列的肽,而原始蛋白具有1~J的氨基酸残基并且其残基1为N-末端;
L是任选的接头;
X2是包含原始蛋白1~n氨基酸残基序列的肽;
Y1是包含对应于原始蛋白的n=1到k的残基序列的蛋白质,而原始蛋白具有1到k顺序编码的氨基酸残基并且残基1为N-末端;
Y2是包含原始蛋白的1~n氨基酸残基序列的肽;
L1和L2是任选的肽间隔区;
n是1到J-1的整数;
b,c,和d分别各自为0或1;
a和e之一可以是0或1,前提是a和e二者不能都为0;以及
T1和T2是蛋白质。
另外,本发明涉及包括编码多功能性造血受体激动剂和核苷酸序列的重组表达载体,相关的微生物表达系统和在蛋白质中制备多功能性造血发夹转折的方法,其中该蛋白质稳定性稍差,但仍能折叠。
发现在此研究中所引用的内部断裂点位置只位于蛋白的表面,分布于整个线性序列之中,而没有明显的针对末端或中部的偏倚性(从原始N-末端到断裂点相对距离的变异为总序列长度的大约10~80%)。在这些研究中,连接原始N-和C-末端的接头为0~9个残基。在一种情况下(Yang & Schachman,美国国家科学院院报90:11980-11984,1993),原始C-末端片段的部分序列已被删去,并在截断的C-末端与原始的N-末端间进行连接。诸如甘氨酸和丝氨酸这样的柔性亲水残基常用在接头中。Viguera等(分子生物学杂志247:670-681,1995)对用3或4残基的接头连接原始N-和C-末端进行了比较,3个残基的接头具有更低的热动力学上的稳定性。Protasova等(蛋白质工程7:1373-1377,1994)在连接大肠杆菌二氢叶酸脱氢酶的原始N-末端时使用了3或5个残基的接头,只有3个残基的接头产生了大量的蛋白。
发明概述
本发明的新型造血蛋白由如下通式表示:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1和R2分别选自:
(I)一种多肽,包括:有下述通式的修饰的人G-CSF氨基酸序列:1 10Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
20Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
30 40Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
50Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
60 70Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
120 130Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
150 160Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro(SEQ ID NO:1)其中Xaa在位点1是Thr,Ser,Arg,Tyr或Gly;Xaa在位点2是Pro或Leu;Xaa在位点3是Leu,Arg,Tyr或Ser;Xaa在位点13是Phe,Ser,His,Thr或Pro;Xaa在位点16是Lys,Pro,Ser,Thr或His;Xaa在位点17是Cys,Ser,Gly,Ala,Ile,Tyr或Arg;Xaa在位点18是Leu,Thr,Pro,His,Ile或Cys;Xaa在位点22是Arg,Tyr,Ser,Thr或Ala;Xaa在位点24是Ile,Pro,Tyr或Leu;Xaa在位点27是Asp或Gly;Xaa在位点30是Ala,Ile,Leu或Gly;Xaa在位点34是Lys或Ser;Xaa在位点36是Cys或Ser;Xaa在位点42是Cys或Ser;Xaa在位点43是His,Thr,Gly,Val,Lys,Trp,Ala,Arg,Cys或Leu;Xaa在位点44是Pro,Gly,Arg,Asp,Val,Ala,His,Trp,Gln或Thr;Xaa在位点46是Glu,Arg,Phe,Arg,Ile或Ala;Xaa在位点47是Leu或Thr;Xaa在位点49是Leu,Phe,Arg或Ser;Xaa在位点50是Leu,Ile,His,Pro或Tyr;Xaa在位点54是Leu或His;Xaa在位点64是Cys或Ser;Xaa在位点67是Gln,Lys,Leu或Cys;Xaa在位点70是Gln,Pro,Leu,Arg或Ser;Xaa在位点74是Cys或Ser;Xaa在位点104是Asp,Gly或Val;Xaa在位点108是Leu,Ala,Val,Arg,Trp,Gln或Gly;Xaa在位点115是Thr,His,Leu或Ala;Xaa在位点120是Gln,Gly,Arg,Lys或His;Xaa在位点123是Glu,Arg,Phe或Thr;Xaa在位点144是Phe,His,Arg,Pro,Leu,Gln或Glu;Xaa在位点146是Arg或Gln;Xaa在位点147是Arg或Gln;Xaa在位点156是His,Gly或Ser;Xaa在位点159是Ser,Arg,Thr,Tyr,Val或Gly;Xaa在位点162是Glu,Leu,Gly或Trp;Xaa在位点163是Val,Gly,Arg或Ala;Xaa在位点169是Arg,Ser,Leu,Arg或Cys;Xaa在位点170是His,Arg或Ser;
其中可选择性地删去N-末端1-11个氨基酸和C-末端的1-5个氨基酸;以及其中N-末端直接或通过一个可将N-末端连接到C-末端上的接头连接到C-末端上,并在如下氨基酸位点具有新的C-和N-末端;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-13757-58 95-96 137-13858-59 96-97 138-13959-60 97-98 139-14060-61 98-99 140-14161-62 99-100 141-142
or 142-143;(II)一种多肽,包含:下述通式的修饰的hIL-3氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130(SEQ ID NO:2);其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Ala,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala,或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr,或Leu;Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中可选择性地删去N-末端的1~14个氨基酸和/或从C-末端删去1~15个氨基酸;而其中用Xaa命名的0~44位氨基酸不同于原始(1-133)人白介素-3的相应的氨基酸;以及
并且N-末端直接或通过一种能把N-末端连接到C-末端上的接头(L2)连接到C-末端上并在如下的氨基酸位点具有新的C-和N-末端;
26-27 49-50 83-84
27-28 50-51 84-85
28-29 51-52 85-86
29-30 52-53 86-87
30-31 53-54 87-88
31-32 54-55 88-89
32-33 64-65 89-90
33-34 65-66 90-91
34-35 66-67 91-92
35-36 67-68 92-93
36-37 68-69 97-98
37-38 69-70 98-99
38-39 70-71 99-100
39-40 71-72 100-101
40-41 72-73 101-102
41-42 82-83 102-103
或103-104;或者
(III)一种多肽,包括:具有下述通式的修饰的人c-mpl配体氨基酸序列:SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer1 5 10 15HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro20 25 30 35ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu40 45 50 55ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis115 120 125 130LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal135 140 145 150ArgArgAlaProProThrThrAlaValProSerArgThrSerLeuValLeuThrLeu
155 160 165 170AsnGluLeuProAsnArgThrSerGlyLeuLeuGluThrAsnPheThrAlaSerAla
175 180 185 190ArgThrThrGlySerGlyLeuLeuLysTrpGlnGlnGlyPheArgAlaLysIlePro
195 200 205GlyLeuLeuAsnGlnThrSerArgSerLeuAspGlnIleProGlyTyrLeuAsnArg210 215 220 225IleHisGluLeuLeuAsnGlyThrArgGlyLeuPheProGlyProSerArgArgThr230 235 240 245LeuGlyAlaProAspIleSerSerGlyThrSerAspThrGlySerLeuProProAsn
250 255 260 265LeuGlnProGlyTyrSerProSerProThrHisProProThrGlyGlnTyrThrLeu
270 275 280 285PheProLeuProProThrLeuProThrProValValGlnLeuHisProLeuLeuPro
290 295 300AspProSerAlaProThrProThrProThrSerProLeuLeuAsnThrSerTyrThr305 310 315 320HisSerGlnAsnLeuSerGlnGluGly(SEQ ID NO:3)325 330 332153其中;112位的Xaa被删去或者是Leu,Ala,Val,Ile,Pro,Phe,Trp,或Met;113位的Xaa被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;114位的Xaa被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;115位的Xaa被删去或者是Gln,Gly,Ser,Thr,Tyr,或Asn;和以及其中N-末端直接或通过一种能把N-末端连接到C-末端上,接头(L2)连接到C-末端,在如下氨基酸位点具有新的C-和N-末端;
26-27 51-52 108-109
27-28 52-53 109-110
28-29 53-54 110-111
29-30 54-55 111-112
30-31 55-56 112-113
32-33 56-57 113-114
33-34 57-58 114-115
34-35 58-59 115-116
36-37 59-60 116-117
37-38 78-79 117-118
38-39 79-80 118-119
40-41 80-81 119-120
41-42 81-82 120-121
42-43 82-83 121-122
43-44 83-84 122-123
44-45 84-85 123-124
46-47 85-86 124-125
47-48 86-87 125-126
48-49 87-88 126-127
50-51 88-89 或127-128;或者
(IV)一种多肽,包括:有如下通式的修饰的hIL-3氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130(SEQ ID NO:2)其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Ala,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala,或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr,或Leu;Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中可选择性删去N-末端的1-14氨基酸和/或C-末端的1-15氨基酸;并且由Xaa所指的1-44氨基酸与天然(1-133)人白介素-3的对应氨基酸不同;或者
(V)一种集落刺激因子;并且其中L1是能连接R1到R2的接头,条件是至少R1或R2选自通式(I),(II),(III)的多肽;并且所说造血蛋白可任选地直接以(Met-1), (Ala-1)或(Met-2,Ala-1)启始。
在上述多肽(I)中可形成新的N-末端和C-末端的更优选的断裂位点是:38-39,39-40,40-41,41-42,48-49,53-54,54-55,55-56,56-57,57-58,58-59,59-60,60-61,61-62,62-63,64-65,65-66,66-67,67-68,68-69,69-70,96-97,125-126,126-127,127-128,128-129,129-130,130-131,131-132,132-133,133-134,134-135,135-136,136-137,137-138,138-139,139-140,140-141和141-142。
在上述多肽(I)中可形成新的N-末端和C-末端的最优选的断裂位点是:38-39,48-49,96-97,125-126,132-133和141-142。
在上述多肽(II)中可形成新的N-末端和C-末端的更优选的断裂位点是:28-29,29-30,30-31,31-32,32-33,33-34,34-35,35-36,36-37,37-38,38-39,39-40,66-67,67-68,68-69,69-70,70-71,84-85,85-86,86-87,87-88,88-89,89-90,90-91,98-99,99-100,100-101和101-102。
在上述多肽(II)中可形成新的N-末端和C-末端的最优选的断裂位点是:34-35,69-70和90-91。
在上述多肽(III)或氨基酸序列(SEQ ID NO:256)中可形成新的N-末端和C-末端的更优选的断裂位点是:80-81,81-82,82-83,83-84,84-85,85-86,86-87,108-109,109-110,110-111,111-112,112-113,113-114,114-115,115-116,116-117,117-118,118-119,119-120,120-121,121-122,122-123,123-124,124-125,125-126和126-127。
在上述多肽(III)中或氨基酸序列(SEQ ID NO:256)中可形成新的N-末端和C-末端的最优选的断裂位点是:81-82,108-109,115-116,119-120,122-123和125-126。
附图简述
图1图解说明蛋白的序列重排。原蛋白的N-末端(N)和C-末端(C)通过接头相连或直接相连。蛋白在断裂点处被打开,形成了新的N-末端(新N)和新的C-末端(新-C),结果使蛋白具有新的线性氨基酸序列。重排的分子可按线性分子从头合成,而不是经过连接原始N-末端和C-末端,然后在断裂点处将蛋白断开的步骤形成。
图2显示方法I的图解,为产生新蛋白,其中原蛋白的原始N-末端和C-末端用一接头连接在一起,产生了蛋白的不同N-末端和C-末端。在实施例中显示的序列重排导致了出现一种编码具有新N-末端和新C-末端的蛋白的新基因。新N-末端在原始蛋白97位氨基酸处产生,原始C-末端(氨基酸174位)通过一连接区与氨基酸11位(氨基酸1-10已被删去)相连,而新C-末端在原始序列96位氨基酸处产生。
图3显示方法II的图解,为产生新蛋白,其中原蛋白的原始N-末端和C-末端不用接头连接在一起,产生了该蛋白的不同的N-末端和C-末端。在实施例中显示的序列重排导致了出现一种编码具有新N-末端和新C-末端的蛋白的新基因。新N-末端在原始蛋白97位氨基酸处产生,原始C-末端(氨基酸174位)与原始N-末端相接,而新C-末端在原始序列的96位氨基酸处产生。
图4显示方法III的图解,为产生新蛋白,其中原蛋白的原始N-末端和C-末端用一接头相接,产生了该蛋白的不同的N-末端和C-末端。在实施例中显示的序列重排导致了产生一种编码具有新N-末端和新C-末端的蛋白的基因。新N-末端在原始蛋白的97位氨基酸处产生,原始C-末端(氨基酸174位)通过一连接区与1位氨基酸相连,而新C-末端在原始序列96位氨基酸处产生。
发明详述
本发明包含自共价连接多肽形成的多功能性造血受体激动剂,其中每一种可通过一种不同的和特异的细胞受体起作用,以启动互补性生物活性。造血生成需要一系列复杂的细胞事件,其中干细胞持续产生形成所有主要谱系的成熟细胞大群体。目前至少已知20种调节子具有造血增殖活性。大多数这些增殖调节子仅能在体外刺激一种或另一种类型的集落形成,由每一调节子刺激集落形成的精确类型相当不同。由集落数评价或较重要的由构成逐步形成集落细胞的谱系和成熟类型评价,没有二种调节子能精确地刺激相同类型的集落形成。增殖应答最容易在简化的体外培养系统中进行分析。能辨别的三种相当不同的参数是集落体积的改变、集落数目的改变和细胞谱系。二种或多种因子可对祖细胞起作用,诱导大量的子细胞形成,因而增加了集落体积。二种或多种因子允许祖细胞增殖增加数量,是由于祖细胞的不同亚集合存在专门针对一种因子应答的情况,或者由于某些祖细胞在能在应答前需要二种或多种因子刺激。通过使用二种或多种因子使细胞的另外受体活化有可能增强有丝分裂信号,因为不同的起始信号通路连合形成共同的最终通路,到达细胞核(Metcalf,自然339:27,1989)。其他机制能解释协同作用。例如,如果一种信号通路受限于由第二个因子引起另外的信号通路中介活化的话,那么这种情况会导致非常大的附加应答。在某些情况下,一种受体类型的活化能诱导其他受体的增强表达(Metcalf,血液82:3515-3523,1993)。二种或多种因子比单一的因子会导致出现不同类型的细胞谱系。应用多功能性造血受体激动剂可能具有潜在的临床优势,其原因是不可能由单一因子引起增殖应答。
造血和其他生长因子的受体能分组为相关蛋白的2个不同家族:(1)酪氨酸激酶受体,包括对表皮生长因子、M-CSF(Sherr,血液75:1,1990)和SCF(Yarden等,EMBO J.6:3341,1987)的受体:以及(2)造血受体,这些受体不含有酪氨酸激酶结构域,但在它们的细胞外结构域中显示明显的同源性(Bazan,美国国家科学院院报87:6934-6938,1990)。在后一组中包括红细胞生成素(EPO)(D′andrea等,细胞57:277,1989),GM-CSF(Gearing等,EMBO J.8:3667,1989),IL-3(Kitamura等,细胞66:1165,1991),G-CSF(Fukunaga等,生物化学杂志265:14008-15,1990),IL-4(Harada等,美国国家科学院院报87:857,1990),IL-5(Takaki等,EMBO J.9:4367,1990),IL-6(Yamasaki等,科学241:825,1988),IL-7(Goodwin等,细胞60:941-51,1990),LIF(Gearing等,EMBO J.10:2839,1991)和IL-2(Cosman等,分子免疫学23:935-94,1986)。后一组的大多数受体以异二聚体的高亲和力形式存在。与配体结合后,特异的α-链形成至少和一种其他的受体链(β-链,γ-链)缔合。许多这些因子共同使用共同的受体亚单位。针对GM-CSF、IL-3和IL-5的α-链共同使用相同的β-链(Kitamura等,细胞66:1165,1991),Takaki等,EMBO J.10:2833-8,1991)和针对IL-6、LIF和IL-11的受体复合物共同使用共同的β-链(gp 130)(Taga等,细胞58:573-81,1989;Gearing等,科学255:1434-7,1992)。IL-2、IL-4、IL-7、IL-9和IL-15的受体复合物共同使用共同的γ-链(Kondo等,科学262:1874,1993;Russell等,科学266:1042-1045,1993;Noguchi等,科学262:1877,1993;Giri等,EMBO J.13:2822-2830,1994)。
多重作用的造血因子的应用亦可通过减少对植入产生因子的细胞和它们的诱导系统的需求而具有潜在的优点。如果一种细胞产生因子的能力有限,那么通过降低每种因子的所需浓度和把它们联合使用而减少对产生因子的细胞的需求,这可能是有用的。多重作用的造血因子的应用可降低所需因子的数量,也许会减少发生不良副作用的可能性。
本发明的新化合物由选自下组的一种通式表示:
R1-L1-R2,R2-L1-R1,R1-R2和R2-R1
其中对R1和R2的解释如上。优选R2是一种集落刺激因子,与R1相比具有不同但互补的活性。依靠互补活性意味着增强或改变对另一种细胞调节物应答的活性。R1多肽要么直接要么通过一种接头片段与R2多肽相连接。措词“直接”确定为多功能性造血受体激动剂其多肽连接没有一种肽接头。因而L1代表一种化学键或多肽片段,R1和R2在框中连接到L1上,最常见的L1是一种线性多肽,R1和R2由酰胺键连接到L1上,R1的羧基端与L1的氨基端相连而L1的羧基端与R2的氨基端相连。由于“框内连接”意味着编码R1和R2的DNA的读框之间没有翻译终止或中断。
其他生长因子的非排除性的列表即集落刺激因子(CSFs)是细胞因子、淋巴因子、白介素、造血生成因子,这些因子能与(I)、(II)或(III)相连接,它们包括GM-CSF、G-CSF、c-mpl配体(也称为TPO或MGDF)、M-CSF、红细胞生成素(EPO)、IL-1、IL-4、IL-2、IL-3、IL-5、IL6、IL-7、IL-8、IL-9、IL-10、IL-11、IL-12、IL-13、IL-15、LIF、flt3/flk2配体、人生长激素、B-细胞生长因子、B-细胞分化因子、嗜酸性分化因子和曾称为青灰因子或c-kit配体的干细胞因子(CSF)。另外,本发明包括修饰过的R1或R2分子或者编码这些R1或R2分子的突变或修饰过的DNA序列的应用。本发明也包括多功能性造血受体激动剂,其中R1或R2是hIL-3变异体、c-mpl配体变异体或G-CSF变异体。“hIL-3变异体”定义为已在WO 94/12638、WO 94/12639和WO95/00646专利号公开内容的具有氨基酸替换和/或hIL-3部分缺失的hIL-3分子,以及本领域熟知的其他变异体。“c-mpl配体变异体”定义为在美国申请系列号08/383,035公开内容的具有氨基酸替换和/或c-mpl配体部分缺失的c-mpl配体分子,以及本领域熟知的其他变异体。“G-CSF变异体”定义为在此公开内容的具有氨基酸替换和/或G-CSF部分缺失的G-CSF分子,以及本领域熟知的其他变异体。
一般来说,连接基团(L1)是长度介于1~500个氨基酸的多肽。连接2个分子的接头优选的设计应为(1)允许2分子不依赖对方而折叠和起作用,(2)没有产生能干扰2种蛋白功能结构域的有序二级结构的趋向,(3)具有最小的能与功能性蛋白结构域相互作用的疏水特性以及(4)提供R1和R2空间隔离,这样R1和R2能同时与位于单细胞上的其相应的受体起作用。在柔性蛋白区典型的表面氨基酸包括甘氨酸、天冬酰胺和丝氨酸。实际上任何含甘氨酸、天冬酰胺和丝氨酸的氨基酸序列的置换可望满足上述用作连接序列的标准。其他中性氨基酸如苏氨酸和丙氨酸也可用于接头序列中。另外的氨基酸也可包括在接头中,这是由于在连接序列中添加独特的限制性位点便于多功能性造血受体激动剂的构建。
本发明优选的L1接头包括选自下列通式的序列:(Gly3Ser)n(SEQ ID NO:4),(Gly4Ser)n(SEQ ID NO:5),(Gly5Ser)n(SEQ ID NO:6),(GlynSer)n(SEQ ID NO:7)或(AlaGlySer)n(SEQID NO:8)。
高度柔性接头的一个实施例是存在于丝状噬菌体如噬菌体M13或fd的pIII蛋白中的富含甘氨酸和丝氨酸的间隔区(Schaller等,美国国家科学院院报72:737-741,1975)。该区提供了在pIII表面蛋白的两个结构域之间的柔性长间隔区。间隔区由如下氨基酸序列组成:
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGluGlyGlyGlySerGlu
GlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGlyGlyGlySer
(SEQ ID NO:9).
本发明也包括其中包含内肽酶识别序列的接头。为分离多功能性造血受体激动剂的组分而体外测定它们是否合适折叠具有活性,这些裂解位点可能是有用的。各种内肽酶的实施例包括但不局限于纤维蛋白溶酶、肠激酶、激肽释放酶、尿激酶、组织纤维蛋白溶酶原活化子、梭菌蛋白酶、凝乳酶、胶原酶、Russell′s蝰蛇毒蛋白酶、脯氨酸后裂解酶(postproline)、V8蛋白酶、凝血酶和Xa因子。
来自重链免疫球蛋白IgG、IgA、IgM、IgD或IgE的铰链区的肽连接片段提供了所连接片段之间的角关系。尤其是这些铰链区中用丝氨酸取代半胱氨酸是有用的。本发明的优选接头包括来源于鼠IgGγ2b铰链区的序列,其中半胱氨酸已变换为丝氨酸。这些接头也可包括内肽酶裂解位点。上述接头的实施例包括在下列序列中:
IleSerGluProSerGlyProIleSerThrIleAsnProSerProProSerLys
GluSerHisLysSerPro(SEQ ID NO:10)和
IleGluGlyArgIleSerGluProSerGlyProIleSerThrIleAsnProSer
ProProSerLysGluSerHisLysSerPro(SEQ ID NO:11)
然而,本发明不受所用的连接序列的形式、大小或数目所限制,并且接头的唯一要求是功能上它不干扰多功能性造血受体激动剂的单独分子的折叠和功能。
接头L2的确定
用于R1和/或R2中的接头L2的氨基酸序列长度根据经验或结构信息指导下选出,或结合使用这两种方法选出。
当没有结构信息可参考时,制备用于试验的少量系列接头可用下列设计,其长度有变化以便包括0~50的范围,而其序列选择要与表面暴露(亲水性,Hopp & Woods,分子免疫学20:483-489,1983),Kyte & Doolittle,分子生物学杂志157:105-132;溶剂暴露表面区,Lee & Richards,分子生物学杂志55:379-400,1971)和采用必需的构象而不干扰R1或R2构象的能力(构象柔性;Karplus & Schulz,Naturwissenschaften 72:212-213,1985)相一致。假定每残基2.0~3.8的翻译平均值,这将意味着所测的长度在0~30个残基之间,以0~15个残基为优选范围。上述系列经验的例证是用诸如重复n次的Gly-Gly-Gly-Ser(SEQ ID NO:12)盒式序列构建接头,其中n为1、2、3或4。本领域的技术人员将识别出许多长度或组成有变化的这样序列用作接头,主要考虑是它们并不过长或过短就行(cf.,Sandhu,生物技术重点评述12:437-462,1992);如果它们太长,熵效应有可能使三维折叠不稳定,也有可能使动力学上折叠不可能发生;如果它们太短,它们就有可能因为扭力或空间张力而使分子不稳定。
本领域的技术人员在分析蛋白的结构信息时将会清楚地认识到用末端之间的距离,即定义为c-α碳之间的距离能用于确定所用序列的长度,或至少限定在经验选择接头时必须测定的可能的数目。他们也会清楚地认识到有时会出现这样的情形,肽链末端的位置在来自X-射线衍射或核磁共振色谱资料所做的结构模型中被错误解释,如果真有这种情况,因而就需要考虑这种情况,以适当地估计所需接头的长度。从那些其位置被准确确定的残基中能选出序列接近链末端的2个残基,而它们的c-α碳之间的距离用于计算它们之间接头的大约长度。利用计算出的长度做指导,那么就能选出具有一系列残基数目的接头(用每残基2~3.8计算)。这些接头可包括原始序列,根据需要缩短或延长。当需要延长时,添加的残基可选自上述的柔性和亲水的种类;或者选择性地用一系列接头替换原始序列,一个实施例是上面提到的Gly-Gly-Gly-Ser(SEQ ID NO:12)盒式方法;或者选择性地利用具有合适总长度的原始序列和新序列的结合方式。
R1和R2氨基和羧基末端的确定
通过从原始多肽链中适当选择开始(氨基末端)和结尾(羧基末端)的位置,而用上述的接头序列L2,就能制备出能折叠成生物学活性状态的R1和R2序列。利用下述的指导原则,氨基和羧基端可从涉及断裂点区共有的序列长度之中选出。在许多情况下,选择的新末端会是羧基末端的原始位置直接位于氨基末端的位置之前。然而,本领域的技术人员会清楚地认识到能起作用的区段中任何位置选择末端,选择末端将有效地导致新序列的氨基或羧基部分缺失或添加。
蛋白的原最初的氨基酸序列支配折叠成表达其生物学功能必需的三维结构。本领域的技术人员利用单一蛋白晶体的X射线衍射和蛋白溶液的核磁共振色谱而获得和解释三维结构信息的方法已经熟知。与断裂点区确认有关的结构信息的实施例包括蛋白二级结构的定位和类型(α和3-10个螺旋,平行和反平行β-片层、链反转、转折和环;Kabsch &Scander,生物聚合体22:2577-2637,1983),氨基酸残基可溶性暴露的程度,残基和另一个残基相互作用的范围和类型(Chothia,生物化学年评53:537-572,1984)以及沿多肽链构象的静态和动态分布(Alber & Mathews,酶学方法154:511-533,1987)。在某些情况下,已知有关残基可溶性暴露的附加信息;一个实施例是蛋白表面必需的翻译后糖类附着位点。当实验性结构信息没有或不便得到时,可用的方法是分析最初的氨基酸序列,以预测蛋白的三级和二级结构、溶剂的可及度及转折和环的发生率。如果直接的结构方法不行时,有时亦可用生物学的方法而经验性确定表面暴露;例如为推知表面暴露,利用有限的蛋白水解鉴别链剪切的位点(Gentile & Salvators,欧洲生物化学杂志218:603-621,1993)。因此,利用来自实验得到的结构信息或预测方法(例如,Srinivisan & Rose蛋白:结构、功能和遗传学22:81-99,1995),根据它们是否整合到二级和三级结构的维持之中,可检查亲代的氨基酸序列而划分区段。产生的序列其中区段已知涉及周期性的二级结构(α和3-10螺旋、平行和反平行的β-片层),应避免这样的区段。相似地,所观察或预测的氨基酸序列区段具有低程度的溶解暴露,很有可能这些区段是称为蛋白的疏水核心部分,也应避免选作氨基和羧基的末端。比较而言,那些已知或预测位于表面转折或环上的区段,尤其是那些已知对生物学活性并不需要的区段是定位多肽链末端的优选位点。根据以上标准优选的氨基酸序列的继续片段归属于断裂点区段。
非共价的多功能性造血生长因子
连接2种造血生长因子的替代方法是通过非共价的相互作用。上述复合蛋白能由下面通式之一加以描述:
R1-C1+R2-C2;或C1-R1+C2-R2;C1-R1+R2-C2;或C1-R1+R2-C2。
R1和R2的定义见上。结构域C1和C2要么相同要么不相同的化学结构,典型的是蛋白性的,这些结构能形成非共价特异的连接。C1和C2之间的复合体结果形成R1和R2之间针对每个复合体的一对一的化学计量关系。连接的结构域实施例是转录因子的“亮氨酸拉链”结构域、细菌转录抑制子的二聚化结构域和免疫球蛋白的恒定结构域。共价键分别连接R1和C1以及R2和C2。正如通式中所示,结构域C1和C2能位于它们相应的造血生成因子(R)的N-末端和C-末端。这些多聚化的结构域(C1-和C2)包括那些来自bZIP蛋白家族的成员(Abel等,自然341:24-25,1989;Landshulz等,科学240:1759-1764,1988;Pu等,核苷酸研究21:4348-4355,1993;Kozarides等,自然336:646-651,1988),以及螺旋-环-螺旋的蛋白家族的多聚化结构域(Abel等,自然341:24-25,1989;Murre等,细胞56:777-783,1989;Tapscott等,科学242:405-411,1988;Fisher等,遗传和发育5:2342-2352,1991)。本发明优选的多功能性造血受体激动剂包括集落刺激因子,这些因子凭借翻译的多功能性造血受体激动剂与bZIP家族蛋白Fos和Jun的亮氨酸拉链二聚体化结构域而二聚体化。Jun的亮氨酸拉链结构域能与相同的结构域相互作用。另一方面,Fos的亮氨酸拉链结构域能和Jun的亮氨酸拉链结构域相互作用,但不能和其他的Fos亮氨酸拉链结构域相互作用。Fos和Jun的混合物优先地形成Fos-Jun异二聚体。所以,当与集落刺激因子连接时,Jun结构域能用于指导同源或异源二聚体的形成。如果集落刺激因子偶联体之一作工程化处理拥有Jun亮氨酸拉链结构域,而另一个作工程化处理拥有Fos拉链,就能得到异二聚体的优选形成。
亦可添加另外的肽序列以便于多功能性造血受体激动剂蛋白的纯化或鉴别(如,聚组氨酸)。也可添加高抗原性的肽段,以通过特异的单克隆抗体对多功能性造血受体激动剂蛋白快速分析和方便纯化。
“突变氨基酸序列”、“突变蛋白”、“变异蛋白”、“突变蛋白”或“突变多肽”指的是,由于氨基酸缺失、替换或二者兼而有之,或者故意制取与原序列不同的核苷酸序列编码的,具有与原序列不同的氨基酸序列的一种多肽。“原序列”指的是氨基酸或核苷酸序列与基因或蛋白的野生型或原始形式相一致。
通过它们刺激来自人造血祖细胞的集落形成的能力而对造血生长因子的进行特征描述。形成的集落包括红细胞系、粒细胞、巨核细胞、粒细胞性巨噬细胞以及它们的混合物。起先在灵长目然后在人类中进行的研究表明,许多造血生长因子具有恢复骨髓功能和外周血细胞群体到治疗上有益水平的功能。造血生长因子的许多或全部的这些生物学活性涉及信号转导和高亲和力受体的结合。当与单因子或改善半寿期或降低不良副效应,或者这些特性的联合作用作比较时,本发明的多功能性造血受体激动剂可显示出诸如相似或更大的生物学活性的有用特性。
很小或没有激动剂活性的多功能性造血受体激动剂或许可用作拮抗剂,用作产生抗体的抗原以使用于免疫学或免疫治疗中,用作基因探针或中间体而用于构建其他有用的hIL-3突变蛋白。
本发明的多功能性造血受体激动剂蛋白的生物学活性可由因子依赖细胞系的DNA合成或在体外骨髓测定中统计集落形成单位加以测定。
与单独起作用的造血激动剂相比较,本发明的多功能性造血受体激动剂可能具有改善的治疗特征。例如,相对于其他不具有相似或相应的增加副作用的造血激动剂,本发明的一些多功能性造血受体激动剂可能有相似或更强的生长因子活性。
本发明也包括编码多功能性造血受体激动剂蛋白的DNA序列,基本上相似和基本上执行相同功能的DNA序列以及仅由于遗传密码的简并性而与编码本发明的多功能性造血受体激动剂的DNA不同的DNA序列。在本发明中也包括用于构建突变的DNA和由这些寡核苷酸编码的多肽的寡核苷酸中间体。
本领域现今标准的遗传工程技术(美国专利号4,935,233和Sambrook等,“分子克隆实验手册”,冷泉港实验室,1989)可用于本发明的DNA序列的构建。上述的一种方法是盒式诱变(Wells等,基因34:315-323,1985),其中在质粒中的部分编码序列在2个限制性位点之间部分基因中,被编码所需氨基酸替换的合成寡核苷酸取代。
编码所需基因的互补合成寡核苷酸能相互配对,退火。寡核苷酸的DNA序列除那些与序列替换和/或缺失的部分例外,能编码所需基因的氨基酸的序列。
质粒DNA用所选的限制性内切酶处理,然后连接到退火的寡核苷酸上。连接的混和物用于转化对合适的抗生素有抗性的感受态JM101细胞中。挑取单菌落,通过限制性分析和/或DNA测序检查质粒DNA,以确认质粒拥有所需的基因。
其中至少拥有其他集落刺激因子的DNA序列之一的新型多功能性造血激动剂的DNA序列的克隆可通过使用中间载体完成。替代方法是可将基因直接克隆到含其他基因的载体中。接头和衔接子用于连接DNA序列,以及取代丢失的序列,其中限制性位点在感兴趣的区段内部。因此,编码一条多肽、多肽接头和其他多肽的遗传材料(DNA)插入到适当的表达载体中,用于转化细菌、酵母、昆虫细胞或哺乳类细胞。培养转化的机体,用标准技术分离蛋白。因此所得的产物是通过将一种集落刺激因子由连接区连接到第二种集落刺激因子上而得到的新蛋白。
本发明的另一方面提供用于表达这些新型的多功能性造血受体激动剂的质粒DNA载体。这些载体含有上述的编码本发明新型多肽的新型DNA序列。能转化微生物,表达多功能性造血受体激动剂的合适载体包括表达载体,这些表达载体包括编码根据所用的宿主细胞选择的转录和翻译调节序列相连接的多功能性造血受体激动剂的核苷酸序列。
如上面所述的整合有修饰过的序列载体也包括在本发明中,用于产生多功能性造血受体激动剂多肽。在方法中所用的载体也含有操作性地和本发明的DNA编码序列相连接的选出的调节序列,该序列能指导在所选的宿主细胞中复制和表达。
作为本发明的另一方面,提供一种方法以生产新型的多功能性造血受体激动剂。本发明的方法涉及培养合适的细胞或细胞系,这些细胞已用含编码表达的新型多功能性造血受体激动剂的DNA序列的载体转化。合适的细胞或细胞系可能是细菌细胞。例如,在生物技术领域中,不同的大肠杆菌菌株作为宿主细胞已众所周知。上述菌株的实施例包括大肠杆菌JM101菌株(Yanish-Perron等,基因33:103-119,1985)和MON 105菌株(Obukowicz等,应用环境微生物学58:1511-1523,1992)。在本发明中也包括根据细菌噬菌体Mu而利用针对大肠杆菌的染色体表达载体表达多功能性造血受体激动剂蛋白(Weinberg等,基因126:25-33,1993)。枯草芽孢杆菌的各种菌株也可用在本方法中。本领域的技术人员熟知的许多酵母细胞株用作宿主细胞表达本发明的多肽亦有效。当在大肠杆菌的细胞质中表达时,编码本发明的多功能性造血受体激动剂基因也可这样构建,在基因密码子的5′端添加编码位于蛋白N-末端的Met-2-Ala-1或Met-1的序列。在大肠杆菌细胞质中产生的蛋白N-末端受翻译后修饰的影响,该修饰由甲硫氨酸氨肽酶(Ben Bassat等,细菌杂志169:751-757,1987)和可能由其他的肽端修饰,结果蛋白表达后,甲硫氨酸从N-末端被切去。本发明的多功能性造血受体激动剂可包括在N-末端具有Met-1,Ala-1或Met-2-Ala-1的多功能性造血受体激动剂多肽。这些突变的多功能性造血受体激动剂通过把分泌信号肽融合到N-末端亦可在大肠杆菌中表达。
也适用于本发明的是哺乳动物细胞,如中国仓鼠卵巢细胞(CHO)。在哺乳动物细胞中表达外源基因的一般方法见综述;Kaufman,R.J.1987)遗传工程,原理和方法,第9卷,J.K.Setlow编著,Plenum出版社,组约。构建表达载体,其中能在哺乳动物细胞中起作用的强启动子驱动真核细胞分泌信号肽编码区的转录,从翻译水平来说,表达载体与多功能性造血受体激动剂的编码区相连接。例如,能用诸如pcDNAI/Neo,pRc/RSV和pRc/CMV的质粒(从Invitrogen Corp.,圣地亚哥,加利福尼亚州得到)。真核细胞分泌信号肽编码区可能来自基因本身或来自另一个分泌性哺乳动物蛋白(Bayne,M.L等,美国国家科学院院报84:2638-2642,1987)。构建含基因的载体后,载体DNA被转染进哺乳动物细胞中。例如,上述细胞可能是COS7、HeLa、BHK、CHO、或小鼠L系细胞。例如,细胞能在DMEM培养基(JRH Scientific)中培养。转染细胞后或接着进行抗生素抗性筛选建立稳定的细胞系后进行24~72小时的瞬时表达,分泌到培养基中的多肽通过标准的生化方法重新得到。挑选合适的哺乳动物宿主细胞和转化、培养、扩增、筛选以及产物生产和纯化方法在本领域已众所周知。例如见Gething和Sambrook,自然,293:620-625,1981),或可供选择的文献,Kaufman等,分子细胞生物学,5(7):1750-1759,1985)或Howley等,美国专利号4,419,446。另一种合适的哺乳动物细胞系是猴COS-1细胞系。相似可用的哺乳动物细胞系是CV-1细胞系。
在本发明的方法中,如果需要,可利用昆虫细胞作为宿主细胞。例如见Miller等,遗传工程,8:277-298(Plenum出版社1986),在此引用作为参考。此外,在昆虫细胞中应用杆状病毒载体表达外源基因的一般方法见如下作者所述:Summer,M.D.和Smith,G.E.,1987)-杆状病毒载体和昆虫细胞培养程序的方法手册,得克萨斯农业试验站通报号1555。构建的表达载体包括杆状病毒转移载体,其中杆状病毒强启动子(例如多角体启动子)驱动真核细胞分泌信号肽编码区转录,从翻译水平来说,表达载体与多功能性造血受体激动剂多肽的编码区相连接。例如,能用pVL 1392质粒(从Invitrogen Corp,圣地亚哥,加利福尼亚州得到)。构建携带编码多功能性造血受体激动剂多肽的基因的载体后,该DNA 2微克和杆状病毒DNA 1微克(见Summers和Smith,1897)共转染到昆虫SF9细胞株中。携带有多功能性造血受体激动剂的纯重组杆状病毒用于转染如培养在Excell 401无血清培养基(JRHBiosciences,Lenexa,Kansas)中的细胞。分泌到培养基中的多功能性造血受体激动剂可通过标准的生化方法重新得到。来自表达多功能性造血受体激动剂蛋白的哺乳动物细胞或昆虫细胞的上清,用任一种系列的商业浓缩部件首先进行浓缩。
本发明的多功能性造血受体激动剂可用于治疗其特征是造血系统的髓样、红细胞样、淋巴样或巨核细胞的水平降低,或者其水平合并降低的疾病。此外,它们可用于活化成熟的髓样或淋巴样的细胞。在这些情况中,用本发明的多肽治疗敏感的是白细胞减少病,该病是在外周血中循环的白细胞(白色细胞)数量减少。白细胞减少症可由接触某些病毒或射线诱发。这通常是各种形式的癌症治疗如接触化疗药物、辐射以及各种形式的感染或出血的副作用。用本发明的这些多功能性造血受体激动剂治疗白细胞减少可避免用目前所用的药物治疗引起的不需要的副作用。
本发明的多功能性造血受体激动剂可用于治疗中性白细胞减少,以及如用于治疗下列情形的疾病;再生障碍性贫血、周期中性白细胞减少症、自发性中性白细胞减少症、先天性白细胞颗粒异常综合征、系统性红斑狼疮(SLE)、白血病、骨髓发育不良综合征和骨髓纤维变性。
本发明的多功能性造血受体激动剂可用于治疗或预防血小板减少症。目前对血小板减少症唯一的疗法是血小板输血,该法费用昂贵、伴有感染(HIV,HBV)和同种异体免疫的严重风险。多功能性造血受体激动剂可减轻或减少对血小板输血的需求。严重的血小板减少症可由诸如Fanconi′s贫血、Wiscott-Aldrich或May Hegglin综合征的遗传缺陷引起。获得性血小板减少症可由如在免疫性血小板减少性紫癜、系统性红斑狼疮、溶血性贫血或胎儿母体不相容性产生的自身或同种抗体引起。此外,脾肿大、散发性血管凝固、血栓性血小板减少性紫癜、感染或修复性心瓣也可引起血小板减少症。严重的血小板减少症也可由化疗和/或放射治疗或癌引起。血小板减少症也可由癌、淋巴瘤、白血病或纤维化所致的骨髓侵袭引起。
本发明的多功能性造血受体激动剂可用于在外周血中的造血祖细胞和干细胞的动员。已表明来源于祖细胞的外周血在重新组成病人体中安置自身骨髓移植中是有效的。包括G-CSF和GM-CSF的造血生长因子已被表明能增强在外周血中循环的祖细胞和干细胞的数量。这简化了收集外周干细胞的过程,通过减少所需的pheresis数量而显著地降低该操作的费用。多功能性造血受体激动剂可用于干细胞的动员,进一步增强外周干细胞移植的效能。
本发明的多功能性造血受体激动剂也可用于造血祖细胞和干细胞的离体扩增。集落刺激因子(CSF)如hIL-3已被单独使用,和其他CSF共同使用,或者骨髓移植继以高剂量化疗时联合使用,以治疗常是化疗处理的结果而出现的中性白细胞减少症和血小板减少症。然而,严重的中性白细胞减少和血小板减少的周期并不能完全消除。髓细胞谱系,包括单核细胞(巨噬细胞)、粒细胞(包括嗜中性细胞)和巨核细胞,在预防感染和对生命有危险的出血中是关键的。中性白细胞减少症和血小板减少症也可能是疟疾、遗传紊乱、药物、毒素、辐射和许多如常规的肿瘤治疗的治疗处理的结果。
骨髓移植已用于治疗这种病人群体。然而,涉及应用骨髓重新构成遭到损害的造血系统的几个问题包括:1)在骨髓、脾或外周血中干细胞的数量是有限的,2)移植物抗宿主疾病,3)移植排斥和4)可能传染肿瘤细胞。在骨髓、脾和外周血中干细胞占有核细胞中非常小的百分率。很明显存在的效量应答使较多数量的干细胞增强造血的恢复。因此,体外干细胞的扩增会增强造血的恢复和病人的成活率。来自同种供体的骨髓用于提供作移植的骨髓。不过,移植物抗宿主病和移植排斥限制了骨髓移植,甚至在与同胞供体HLA配对的受体中也存在这些问题。对同种骨髓移植的一种替代方法是自体骨髓移植。在自体骨髓移植中,髓损毁疗法(myeloablative therapy)如高剂量化疗前收获一些病人自身的骨髓,在疗法之后输回病人体内。自体移植消除了移植对宿主疾病和移植排斥的危险。可是,自体骨髓移植仍存在骨髓中干细胞数量有限和可能传染肿瘤细胞方面的问题。干细胞数量有限能被干细胞的离体扩增克服。此外,为了减少骨髓移植的肿瘤细胞污染,可根据存在的如CD34+的特异表面抗原,特异地分离干细胞。
关于分离干细胞、CD 34+细胞,培养有造血因子的细胞,应用细胞治疗造血紊乱的病人和应用造血因子作细胞扩增和基因治疗,下列的专利含有更为详细的技术。
专利5,061,620叙述包含人造血干细胞的组合物,人造血干细胞通过从献出的细胞中分离干细胞而供给。
专利5,199,942一种自体造血细胞移植的方法,该方法包括:(1)从病人中获得造血祖细胞;(2)用选自IL-3、flt3配体、c-kit配体、GM-CSF、IL-1、GM-CSF/IL-3融合蛋白以及其联合使用的生长因子离体扩增细胞;(3)给病人使用细胞制品。
专利5,240,856叙述一种包括自动控制细胞分离过程装置的细胞分离器。
专利WO 91/16116描述从细胞混合物中选择性地分离和分开靶细胞的装置和方法。
专利91/18972叙述体外培养骨髓细胞的方法,该方法用一种中空纤维生物反应器培养悬浮的骨髓细胞。
专利WO 92/18615叙述用于移植,在含有细胞因子特异混合物的培养基中维持和扩增骨髓细胞的一种方法。
专利WO 93/08266描述一种选择性地扩增干细胞的方法,该方法包括(a)从其他细胞中分离CD 34+干细胞和(b)在选择性培养基中培养分离的细胞,这样干细胞能选择性地扩增等步骤。
专利WO 93/18136描述一种体外维持来自外周血的哺乳动物细胞的方法。
专利WO 93/18648叙述一种包括人嗜中性前体细胞的组合物,该组合物具有高含量的成髓细胞和早幼粒细胞,以用于治疗遗传或获得性中性白细胞减少症。
专利WO 94/08039描述一种通过选择表达c-kit蛋白的细胞而富集人造血干细胞的方法。
专利WO 94/11493描述一种CD 34+、小体积的干细胞群体,这些细胞用一种逆流(counterflow)流动淘洗方法分离。
专利WO 94/27698叙述一种结合免疫亲和分离和连续流动离心分离而从异源细胞混合物中选择性地分离有核异源细胞群体的方法。
专利WO 94/25848描述一种收集和操作靶细胞的细胞分离装置。
在含IL-1a、IL-3、IL-6或GM-CSF的培养物中,长期培养从人骨髓高度富集的造血祖细胞的CD 34+前体细胞的方法,在Brandt等,J.Clin.Invest.86:932-941,1990)中已被讨论。
本发明的一个方面提供一种选择性地离体扩增干细胞的方法。措词“干细胞”指的是全能造血干细胞以及从骨髓、脾或外周血分离的早期前体细胞和祖细胞。措词“扩增”指的是细胞的分化和增殖。本发明提供一种选择性地离体扩增干细胞的方法,该方法包括如下步骤:(a)从其他细胞中分离干细胞,(b)用含多功能性造血受体激动剂蛋白的选择性培养基培养所分离的干细胞以及(c)收获干细胞。干细胞以及注定成为嗜中性细胞、红细胞、血小板等的定型祖细胞,依靠存在或缺乏特殊的祖细胞标志抗原,如存在于这些细胞表面的CD 34,和/或依靠形态学特征可从大多数其他细胞中区分出来。已报道高度富集人干细胞部分的表型为CD 34+、Thy-1+和lin-,但可以理解本发明并不局限于扩增这种干细胞群体。富集的人CD 34+干细胞部分能通过许多已报道的方法分离,这些方法包括利用直接针对表面抗原如CD 34+的抗体的亲和柱或珠、磁性珠或流式细胞术。此外,如逆流淘洗的物理分离方法可用于富集造血祖细胞。CD 34+祖细胞是异质的,可根据存在或缺乏和细胞表面相关分子有关的不同谱系的共表面特征分为几种亚群。最不成熟的祖细胞不表达任何已知的如HLA-DR或CD 38的谱系相关标志,但它们可表达CD 90(thy-1)。其他表面抗原如CD 33、CD 38、CD 41、CD 71、HLA-DR或c-kit也能用于选择性地分离造血祖细胞。分离的细胞在培养瓶、无菌袋或中空纤维中用选择培养基培养。为选择性地扩增细胞,可使用各种集落刺激因子。被用于离体扩增骨髓细胞的代表性因子包括c-kit配体、IL-3、G-CSF、GM-CSF、IL-1、IL-6、IL-11、flt-3配体或联合使用。干细胞的增殖在培养前或后来的过程中通过统计干细胞和其他细胞的数量、通过标准技术(如血细胞计数器、CFV、LTCTC)或通过流式细胞术加以监控。
已经报道离体扩增干细胞的几种方法是利用许多选择方法和应用各种集落刺激因子的扩增方法。这些集落刺激因子包括c-kit配体(Brandt等,血液83:1507-1514[1994],Mckenna等,血液86:3413-3420[1995])、IL-3(Brandt等,血液83:1507-1514[1994],Sato等,血液82:3600-3609[1993])、G-CSF(Sato等,血液82:3600-3609[1993])、GM-CSF(Sato等,血液82:3600-3609[1993])、IL-1(Muench等,血液81:3463-3473[1993])、IL-6(Sato等,血液82:3600-3609[1993])、IL-11(Lemoli等,实验血液学21:1668-1672[1993],Sato等,血液82:3600-3609[1993])、flt-3配体(Mckenna等,血液86:3413-3420[1995])和/或这些因子的组合使用(Brandt等,血液83:1507-1514[1994],Haylock等,血液80:1405-1412[1992]、Koller等,生物技术11:358-363[1993],(Lemoli等,实验血液学21:1668-1672[1993]),Mckenna等,血液86:3413-3420[1995],Muench等,血液81:3463-3473[1993],Patchen等,生物治疗7:13-26[1994],Sato等,血液82:3600-3609[1993],Smith等,实验血液学21:870-877[1993],Steen等,干细胞12214-224[1994],Tsujino等,实验血液学21:1379-1386[1993])。在单个集落刺激因子中,已表明hIL-3是最有力的扩增外周血CD 34+细胞的因子之一(Sato等,血液82:3600-3609[1993],Kobayashi等,血液73:1836-1841[1989])。然而,已表明单独因子没有像多种因子联合使用一样有效。本发明提供利用比单一因子单独使用更有效的多功能性造血受体激动剂离体扩增的方法。
本发明的另一方面提供维持和扩增造血前体细胞的方法,该方法包括把细胞接种到含如下培养基的培养容器中,该培养基通过接触如HS-5基质细胞系处良好状态(专利号WO 96/02662,Roecklein和Torok-Strob,血液85:997-1105,1995),补加有本发明的多功能性造血受体激动剂。
生长因子的另一个具体临床应用是体外激活造血祖细胞和干细胞而用作基因治疗。由于造血祖细胞寿命长,而其子细胞遍布于整个人体中,造血祖细胞是作离体基因转染的最佳候选者。为了使感兴趣的基因结合进入造血祖细胞或干细胞的基因组中,人们需要刺激细胞分裂和DNA复制。造血干细胞以非常低的效率循环,这意味着生长因子可能在促进基因转导中是有用的,因而加强基因治疗的临床应用前景。基因治疗的潜在应用(见综述Crystal,科学270:404-410[1995])包括:1)治疗许多先天性的代谢紊乱和免疫缺损(Kay和Woo,遗传学进展10:253-257[1994]),2)神经性紊乱(Friedmann,遗传学进展10:210-214[1994]),3)癌(Culver和Blaese,遗传学进展10:174-178[1994])和4)传染病(Gilboa和Smith,遗传学进展10:139-144[1994])。
已有本领域技术人员熟知的种种方法,把遗传材料导入到宿主细胞中。已出现许多病毒和非病毒的载体把治疗基因转移到原初细胞中。依靠病毒的载体包括;1)复制缺陷的重组逆转录病毒(Boris-Lawrie和Temin,Curr.Opin.Genet.Dev.3:102-109[1993],Boris-Lawrie和Temin,纽约科学院年评716:59-71[1994],Miller,Current Top.Microbiol.Immunol.158:1-24[1992]),以及复制缺陷的重组腺病毒(Berkner,生物技术6:616-629[1988],Berkner,Current Top.Microbiol.Immunol.158:39-66[1992],Brody和Crystal,纽约科学院年评716:90-103[1994])。基于非病毒的载体包括蛋白/DNA复合体(Cristiano等,美国国家科学院院报90:2122-2126[1993],Curiel等,美国国家科学院院报88:8850-8854[1991],Curiel,纽约科学院年评716:36-58[1994]),电穿孔和脂质体介导的转移,如阳离子脂质体(Farhood等,纽约科学院年评716:23-35[1994])。
本发明提供一种扩增造血细胞现存方法的改进方法,引入了新的遗传材料,因为本发明提供的方法是利用具有改善的生物学活性的多功能性造血受体激动剂蛋白,这些活性包括任何单一的集落刺激因子中未看到过的活性。
许多药物可能引起骨髓抑制或造血缺损。上述药物的实施例为AZT、DDI、用于化疗的烷化剂和抗代谢药、如氯霉素、青霉素、甘昔洛韦柔红霉素的抗生素、磺胺药、酚噻嗪、镇静剂如氨甲丙二酯、镇痛药如氨基比林和去甲氨基比林、抗惊厥药如二苯乙内酰胺或酰胺咪嗪、抗甲状腺药如丙基硫氧嘧啶和甲巯咪唑以及利尿药。本发明的多功能性造血受体激动剂可用于预防或治疗用以上药物治疗的病人中常发生的骨髓抑制或造血缺损。
造血缺损也可能因病毒、微生物或寄生虫感染的结果以及治疗肾病或肾衰竭如透析的结果而发生。本发明的多功能性造血受体激动剂可用于治疗上述造血缺损。
治疗造血缺损可包括给病人施用含多功能性造血受体激动剂药用组合物。本发明的多功能性造血受体激动剂可用于造血前体细胞的活化和扩增,该法在把这些细胞注射到病人之前体外使用本发明的多功能性造血受体激动剂蛋白处理那些细胞。
用本发明的多功能性造血受体激动剂治疗也可有效地影响各种如在T和B细胞中的免疫缺损,或者如类风湿性关节炎的免疫紊乱。免疫缺损可能是如HTLVI、HTLVII、HTLVIII病毒感染。严重地接触辐射、癌治疗的结果,或者是其他医学治疗的结果。本发明的多功能性造血受体激动剂单独或和其他集落刺激因子联合也用于治疗其他的血液细胞缺损,包括血小板减少症(血小板缺损)或贫血。这些新型多肽的其他用途是体内或离体治疗骨髓移植恢复的病人和用标准方法产生的作诊断或治疗用途的单克隆和多克隆抗体的开发。
本发明的其他方面是治疗参见上述疾病的方法和治疗组合物。上述组合物在和药学上可接受的载体混合物中包含一种或多种本发明的多功能性造血受体激动剂的治疗有效量。这种组合物可肠胃外、静脉内或皮下施用。如果施用时,在本发明中所用的治疗组合物优选的是无致热原、肠胃外可接受的水溶液形式。上述肠胃外可接受的蛋白溶液的制备,具有适当的pH、等渗性、稳定性等,本领域的技术均能达到。
治疗上述疾病的方法中涉及的剂量方案由主治医师确定,要考虑各种减轻药物作用的因素,如病人的病况、体重、性别和饮食,任一感染的严重性,施用时间和其他临床因素。一般来说,一天的方案是每公斤体重0.2-150μg/kg的多功能性造血受体激动剂蛋白。相对于给出的多功能性造血受体激动剂蛋白的活性调整剂量,注意剂量方案包括每天每公斤体重低至0.1微克及高至1毫克的剂量并不是不合理的。另外,可能存在具体的情况,此时多功能性造血受体激动剂的剂量比每公斤体重0.2-150微克的范围被调整到更高或更低。这些方案包括和其他集落刺激因子或IL-3变异体或生长因子一起施用,和化疗药物和/或放射法一起施用;使用糖基化的多功能性造血受体激动剂蛋白;以及本节中早些时候提到的各种病人相关组织。同时或顺序和本发明的多肽共同施用的其他适当的集落刺激因子(CSF)、细胞因子、淋巴因子、造血生长因子和白介素,非排除性列出的以上因子包括GM-CSF、G-CSF、c-mpl配体(也称为TPO或MGDF)、M-CSF、红细胞生成素(EPO)、IL-1、IL-4、IL-2、IL-3、IL-5、IL-6、IL-7、IL-8、IL-9、IL-10、IL-11、IL-12、IL-13、IL-15、IL-16、LIF、fl3/flk2配体、B细胞生长因子、B细胞分化因子和嗜酸性细胞分化因子,也称为青灰因子或c-kit配体的干细胞因子(SCF),或者这些因子的联合物。调整上述所用的剂量以补偿在治疗组合物中的附加组分。被治疗病人的疗效进展通过血液学特征如分化细胞计数等的周期性评估加以监控。
材料和方法
除非在他处注明,所有特殊的化学品从西格玛公司(圣·路易斯,MO)得到。限制性内切酶和T4 DNA连接酶从New England Biolabs(Beverly,MA)或Boehringer Mannheim(Indianapolis,IN)得到。
大肠杆菌菌株的转化
大肠杆菌菌株如DH5αTM(Life Technologies,Gaithersburg,MD)和TG1(Amersham Corp.,Arlington Heights,IL)被用于连接反应的转化,是转染哺乳动物细胞的质粒DNA的来源。大肠杆菌菌株如JM101(Yanisch-Perron等,基因,33:103-119,1985)和MON 105(Obukowicz等,Appl.and Envir.Micr.,58:1511-1523,1992)能用于在细胞质或周质腔中表达本发明的多功能性造血受体激动剂。
MON 105 ATCC#55204:F-,lambda-,IN(rrnD,rrF)l,rpoD+,rpoH358
DH5αTM:F-,phi80dlaczdeltaM15,δ(lacZYA-argF)U169,deoR,recAl,endAl,hsdR17(rk-,mk+),phoA,supE44lamda-,thi-1,gyrA96,relAl
TG1:δ(lac-pro),supE,thi-1,hsdD5/F′(traD36,proA+B+,lacIq,lacZdeltaM15)
JM101 ATCC#33876:δ(pro lac),supE,thi,F′(traD36,proA+B+,lacIq,lacZdeltaM15)
DH5αTM亚克隆用细胞购买时为感受态细胞,用厂家的操作步骤已准备好可用于转化,而两种大肠杆菌菌株TG1和MON 105要用氯化钙法变为吸收DNA的感受态。典型的操作是,20~50mL的细胞生长在LB培养基(1%细菌培养用蛋白胨,0.5%细菌培养用酵母浸出汁,150mM氯化钠)中,长至用Baush & Lomb分光光度计(Rochester,NY)测定600纳米(OD 600)的光密度值大约为1.0的密度。通过离心收集细胞,细胞悬浮在五分之一培养体积的氯化钙溶液中(50mM CaCl2,10mM Tris-Cl,pH7.4),放在4℃30分钟。细胞再次通过离心被收集,重悬于十分之一培养体积的氯化钙溶液中。连接好的DNA加到0.2mL这些细胞液中,样品放在4℃30~60分钟。样品移至42℃2分钟,在37℃摇动样品1小时前加1.0mL的LB。来自这些样品的细胞分散在平板上(LB培养基加1.5%bacto-琼脂),若筛选抗氨苄霉素的转化体,平板中含氨苄霉素(100微克/mL,μg/mL);或者筛选抗壮观霉素的转化体,平板中含壮观霉素(75μg/mL)。平板在37℃下培养过夜。
挑取菌落,接种到添加了合适抗生素(100μg/mL氨苄霉素或75μg/mL壮观霉素)的LB中,然后在37℃摇动生长。
创制具有新N-末端/C-末端基因的方法
方法I.产生含接头区(L2)具有新N-末端/C-末端的基因
具有新的N-末端/C-末端含连接区(L2)与原始C-末端和N-末端不同的基因,基本上按在L.S.Mullins等,美国化学学会杂志116,5529-5533,1994)所描述的方法制得。聚合酶链反应(PCR)扩增的多种步骤用于重排编码蛋白原初氨基酸序列的DNA序列。这些步骤在图2说明。
第一步,第一套引物(“新起点”和“连接起点”)用于从原始基因序列中产生和扩增DNA片段(“片段起点”),该DNA片段含编码新蛋白的新N-末端部分后续是连接原始蛋白的N-末端和C-末端接头(L2)的序列。第二步,第二套引物(“新终止点”和“接头终止点”)用于从原始基因序列产生和扩增DNA片段(“片段终止点”),该DNA片段编码如上所用的相同接头,后续从新蛋白的新C-末端部分。设计“新起点”和“新终止点”引物包括允许新基因克隆到表达质粒中的合适的限制性位点。典型的PCR条件是95℃一个循环融解2分钟;94℃变性1分钟,50℃退火1分钟和72℃延伸1分钟共进行25个循环;加72℃延伸7分钟的1个循环。用Perkin Elmer GeneAmp PCR Core试剂盒。100μl反应液含每种引物100pmol和1μg模板DNA;1×PCR缓冲液,200μM dGTP,200μM dATP,200μM dTTP,200μMdCTP,2.5单位AmpliTaq DNA聚合酶和2mM MgCl2。PCR反应在型号480的DNA热循环仪中进行(Perkin Elmer Corporalion,Norwalk,CT)。
在接头区有互补序列和对位于接头的二边的2个氨基酸有编码序列的“片段起点”和“片段终点”在第三步PCR反应中连接在一起,以形成编码新蛋白的全长基因。“片段起点”和“片段终点”的DNA片段在1%TAE凝胶中分离,用溴化乙锭染色和Qiaex凝胶抽提试剂盒(Qiagen)分离。这些片段以等摩尔量结合,在70℃加热10分钟然后缓慢冷却以通过它们在“接头起点”和“接头终点”的共有序列退火。第三步PCR反应,“新起点”和“新终点”的引物加到退火的片段中,以产生和扩增全长的新N-末端/C-末端的基因。典型的PCR条件是95℃1个循环融解2分钟;94℃变性1分钟,60℃退火1分钟,72℃延伸1分钟共25个循环;加72℃延伸1分钟的1个循环。用PerkinElmer GeneAmp PCR Core试剂盒。100μl反应液含每种引物100pmol,大约0.5μg DNA和1×PCR缓冲液,200μM dGTP,200μMdATP,200μM dTTP,200μM dCTP,2.5单位AmpliTaq DNA聚合酶和2mM MgCl2。用Wizard PCR Preps试剂盒(Promega)纯化PCR反应液。
方法II.产生具有新N-末端/C-末端没有连接区的基因
没有连接原始N-末端和C-末端接头的新N-末端/C-末端的基因用PCR扩增的二步反应和1个平末端连接制成。反应步骤在图3说明。第一步,引物(“新起点”和“P-bl起点”)用于从原始基因序列产生和扩增DNA片段(“片段起点”),该DNA片段含编码新蛋白的新N-末端部分的序列。第二步,引物(“新终点”和“P-bl终点”)用于从基因序列产生和扩增DNA片段(“片段终点”),该DNA片段含新蛋白的新C-末端部分的序列。设计“新起点”和“新终点”的引物包括允许新基因克隆到表达载体中的限制性位点。典型的PCR条件是95℃1个循环融解2分钟;94℃变性1分钟,50℃退火45秒,72℃延伸45秒,共25个循环。按厂家推荐的条件用Deep Vent聚合酶(NewEngland biolabs)以降低突出的发生率。“P-bl起点”和“P-bl终点”的引物在5′端被磷酸化,有助于下一步“片段起点”和“片段终点”互相之间的平末端连接。100μl反应液含150pmol的每种引物和1μg的模板DNA;1×Vent缓冲液(New England Biolabs),300μMdGTP,300μM dATP,300μM dTTP,300μM dCTP和1单位的Deep Vent聚合酶。PCR反应在型号480的DNA热循环仪(PerkinElmer Corporation,Norwalk,CT)中进行。PCR反应产物用WizardPCR Preps试剂盒(Promega)纯化。
设计的引物包括允许克隆新基因到表达载体中的合适的限制性位点。典型的“片段起点”被设计为产生NcoI限制性位点,而“片段终点”被设计为产生HindIII限制性位点。限制性消化反应液用Magic DNAClean-up系统试剂盒(Promega)纯化。起点和终点片段在1%TAE凝胶中分离,用溴化乙锭染色,用Qiaex凝胶提取试剂盒(Qiagen)分离。这些片段和pMON 3934的~3800碱基对NcoI/HindIII载体片段的末端结合和退火,反应在50℃加热10分钟然后使其缓慢冷却进行。三个片段用T4 DNA连接酶(Boehringer Mannheim)连接在一起。结果为含全长新的N-末端/C-末端基因的质粒。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(Life Technologies,Gaithersburg,MD)。纯化质粒DNA,按下列方法确认序列。
方法III.用串联重复方法产生新N-末端/C-末端的基因
新N-末端/C-末端的基因可根据在R.A.Horlick等,蛋白质工程5:427-431,1992)中所描述的方法制成。聚合酶链反应(PCR)扩增新N-末端/C-末端的基因用串联式重复的模板DNA进行。其步骤在图3说明。
串联重复模板DNA用克隆法产生,含有由编码连接2个拷贝基因的原始N-和C-末端的接头的DNA序列隔开的2个拷贝基因。特殊的引物对用于从串联重复模板DNA上产生和扩增全长新的N-末端/C-末端的基因。设计这些引物包括允许新基因克隆到表达载体中的合适的限制性位点。典型的PCR条件是95℃1个循环融解2分钟;94℃变性1分钟,50℃退火1分钟和72℃延伸1分钟,共25个循环;加72℃延伸7分钟的1个循环。用Perkin Elmer GeneAmp PCR Core试剂盒(Perkin Elmer Corporation,Norwalk CT)。100μl反应液含100pmol的每种引物和1μg模板DNA;1×PCR缓冲液,200μM dGTP,200μM dATP,200μM dTTP,200μM dCTP,2.5单位AmpliTaqDNA聚合酶和2mM MgCl2。PCR反应在型号480的DNA热循环仪(Perkin Elmer Corporation,Norwalk,CT)中进行。PCR反应液用Wizard PCR Preps试剂盒(Promega)纯化。
把新N-末端/C-末端基因克隆到多功能受体激动剂表达载体中
新N-末端/C-末端基因用限制性内切酶消化,以产生适合插入到含另一种集落刺激因子基因的表达载体中的末端。这种表达载体也同样用限制性内切酶消化而形成相容末端。纯化后,基因和载体DNA用T4DNA连接酶结合和连接。部分连接反应液用于转化大肠杆菌。纯化质粒DNA,测序以证实正确的插入。培养正确的克隆以表达蛋白。
DNA分离和特性描述
本领域的技术人员熟知的许多不同方法和使用可购买到的商品化试剂盒分离质粒DNA。在此说明少数上述方法。用Promega WizardTMMiniprep试剂盒(Madison,WI),Qiagen QIAwell质粒分离试剂盒(Chatsworth,CA)或Qiagen Plasmid Midi试剂盒分离质粒DNA。这些试剂盒遵循相同的一般程序分离质粒DNA。简言之,细胞用离心法(5000×g)沉淀,用顺序的NaOH/酸处理释放质粒DNA,细胞碎片用离心(1000×g)移去。上清(含质粒DNA)加到含结合DNA树脂的柱上,洗柱,用TE洗脱质粒DNA。筛选含感兴趣的质粒菌落后,大肠杆菌细胞接种到加适量抗生素50-100ml的LB中,在振荡的空气培养箱中37℃下生长过夜。纯化的质粒DNA用于DNA测序,进一步的限制性酶消化,另外的DNA片段亚克隆和转染到哺乳动物、大肠杆菌或其他细胞中。
序列的确认
纯化的质粒DNA重新悬浮在dH2O中,用Bausch and lombSpectronic 601紫外分光光度计测定260/280nM的吸光值定量。DNA样品用ABI PRISMTM DyeDeoxyTM终止测序化学法(Perkin ElmerCorporation的应用生物系统分公司,林肯市,CA)试剂盒(批号401388或402078)测序,根据厂家的建议通常加5%DMSO到测序混合液中而修改方法。按照建议的扩增条件,测序反应在型号480的DNA热循环仪(Perkin Elmer Corporation,Norwalk,CT)中进行。样品用Centri-SepTM spin柱(Princeton Separations,Adelphia,NJ)移去过量的染料终止剂而被纯化,然后冻干。标记上荧光染料的测序反应液重新悬浮在去离子的甲酰胺中,用ABI型号373A的自动DNA测序仪在变性的4.75%聚丙烯酰胺8M尿素凝胶上测序。重叠的DNA序列片段用Sequencher v2.1 DNA分析软件(基因密码公司,Ann Arbor,MI)分析,组合成主DNA毗连序列群。
多功能性受体激动剂在哺乳动物细胞中表达
哺乳动物细胞转染/生产的条件培养基
BHK-21细胞系从ATCC(Rockville,MD)获得。细胞培养在Dulbecco′s修改Eagle培养基(DMEM/高葡萄糖)中,补加2mM(mM)L-谷氨酰胺和10%胎牛血清(FBS)。这种配方被命名为BHK生长培养基。选择培养基是补加453单位/mL的潮霉素B(Calbiochem,SanDieqo,CA)的BHK生长培养基。BHK-21细胞系以前已用HSV转活化蛋白VP16转染过。细胞转染特征稳定,能转活化在质粒pMON 3359中存在的IE 110启动子(见Hippenmeyer等,生物技术pp 1037-1041,1993)。VP16蛋白驱使插入在IE 110启动子之后的基因表达。表达转活化的VP16蛋白的BHK-21细胞命名为BHK-VP16。质粒pMON1118(见Highkin等,家禽科学,70:970-981,1991)表达从SV40启动子表达潮霉素抗性基因。可从ATCC得到相似的质粒,pSV2-hph。
转染前BHK-VP16细胞以每皿3×105个细胞接种到60毫米(mm)组织培养皿中,培养24小时。在含有感兴趣基因的质粒DNA10μg,潮霉素抗性质粒pMON 1118 3μg和每皿Gibco-BRL“LIPOFECTAMINE”80μg的3mL“OPTIMEM”TM(Gibco-BRL,Gaithersburg,MD)中,转染细胞16小时。接着吸去培养基,重加3mL生长培养基。转染后48小时,从每皿中收集培养基,进行活性测定(瞬时条件培养基)。用胰酶-EDTA使细胞从皿上脱离,细胞以1∶10稀释,转移到含10mL选择培养基的100mm组织培养皿中。在选择培养基中约7天后,抗性细胞长成直径为几毫米的集落。集落用滤纸(剪成约与克隆相同的体积,浸在胰酶/EDTA中)从皿上脱离,转移到24孔板的各个孔中,每孔含1mL选择培养基。克隆长到汇合后,重新检测条件培养基,阳性克隆到生长培养基中扩大。
多功能性受体激动剂在大肠杆菌中表达
在型号G25来自New Brunswick Scientific(Edison,Neco Jersey)的空气培养箱中,包含感兴趣质粒的大肠杆菌MON 105或JM 101菌株在加酪蛋白氨基酸的M9培养基中37℃下振荡培养。OD 600值监控生长,直到其值达到1.0,此时加溶在0.1N NaOH中的萘啶酮酸(10mg/mL)至终浓度50μg/mL。然后培养物在37℃下摇动另外的3至4个小时。整个培养期间维持高度通气,以便获得大量产生所需的基因产物。在光学显微镜下对细胞作包含体(IB)存在的检查。吸取1mL培养等份物进行蛋白含量分析,该分析方法是煮沉淀的细胞,用还原缓冲液处理,然后通过SDS-PAGE电泳(见Maniatis等,分子克隆:实验室手册,1982)。离心培养物(5000×g)以沉淀细胞。
包含体的制备、提取、重新折叠、透析、DEAE层析以及在大肠杆
菌中作为包含体积累的多功能性造血受体激动剂的特征描述
分离包含体:
来自330mL的大肠杆菌培养物的细胞沉淀重浮在15mL的超声缓冲液(10mM 2-氨基-2-(羟甲基)1,3-丙二醇盐酸pH8.0+1mM乙二胺四乙酸(EDTA)中。这些重悬的细胞用超声细胞破碎器(型号W-375,热系统超声公司,Farmingdale,纽约)的微点探头超声破碎。在超声缓冲液中三轮超声接着离心用于破碎细胞,洗包含体(IB)。第一轮超声是3分钟脉冲,后接1分钟脉冲,最后二轮的超声各为1分钟的脉冲。
来自包含体沉淀的蛋白提取和重新折叠:
接着最后离心步骤,IB沉淀重悬在10mL的50mM Tris-HCl,pH9.5,8M尿素和5mM二硫苏糖醇(DTT)中,室温下搅拌约45分钟以使所表达蛋白变性。
提取液转移到含70mL的5mM Tris-HCl,pH9.5和2.3M尿素的烧杯中,温和搅拌4℃暴露在空气中18~48小时,以使蛋白重新折叠。重折叠在Vydac(Hesperia,Ca)C18反向高压液相层析(RP-HPLC)柱(0.46×25cm)上分析监测。含0.1%三氟乙酸(TPA)的40%~65%乙腈的线性梯度用于监测重折叠过程。这种梯度在每分钟1.5mL的流率下过30分钟后形成。一般情况下变性蛋白在梯度中比重新折叠蛋白较晚洗脱下来。
纯化:
重折叠后,污染的大肠杆菌蛋白用酸沉淀法移去。重折叠溶液的pH用15%(v/v)乙酸(HOAc)滴定在pH5.0~pH5.2。该溶液4℃搅拌2小时,然后在12,000×g下离心20分钟以沉淀任何不可溶的蛋白。
来自酸沉淀步骤的上清用分子量截断(MWCO)为3,500道尔顿的Spectra/Pro3膜透析。透析在4升(过量50倍)的10mM Tris-HCl,pH8.0液经2次替换的情况下进行,总时间为18小时。在DEAE层析前透析降低样品的导电性,去除尿素。透析后接着离心样品(12,000×g下20分钟)以沉淀任何不可溶的蛋白。
Bio-Rad Bio-Scale DEAE2柱(7×52mm)用作离子交换层析。层析柱在含10mM Tris-HCl,pH8.0和0~500mM氯化钠(NaCl)梯度的缓冲液中平衡。在平衡缓冲液中,超过45倍柱体积用于洗脱蛋白。整个过程用每分钟1.0mL的流率。收集整个梯度的柱级分(每级分2.0mL),在Vydac(Hesperia,Ca.)C18柱(0.46×25cm)上用RP HPLC分析。用含0.1%三氟乙酸40%~65%乙腈的线性梯度。该梯度在每分钟1.5mL的流速下过30分钟产生。然后混合的组分在4升(过量50~500倍)的10mM乙酸铵(NH4Ac)pH 4.0液经2次替换而被透析,总时间为18小时。透析用分子量截断值3,500道尔顿的Spectra/Pro3膜进行。样品用0.22μM注射过滤器(μStar LB注射过滤器,Costar,Cambridge,Ma.)过滤除菌,然后4℃下贮存。
在某些情况下,折叠的蛋白能用连接到合适基质上的亲和试剂如mAb或受体亚单位亲和纯化。可供选择的方法(或此外),纯化能用许多层析方法的任一种完成,例如:离子交换、凝胶过滤或疏水层析或反相HPLC。
这些和其他蛋白纯化方法的细节描述见酶学方法,182卷‘蛋白纯化指南’Murray Deutscher编著,科学出版社,圣地亚哥,CA(1990)。
蛋白特性描述
纯化的蛋白用RP-HPLC、电子喷射质谱和SDS-PAGE分析。蛋白定量用氨基酸组成法、RP-HPLC和Bradfbrd蛋白测定法进行。在某些情况下,作胰酶肽谱图,结合电子喷射质谱法确认蛋白的特性。
对生物活性的人白介素-3作AML增殖测定
因子依赖的AML 193细胞系从美国典型培养收集保藏中心(ATCC,Rockville,MD)得到。从患急性骨髓性白血病的一位病人的细胞建立的这种细胞系是一种生长因子依赖的细胞系,在添加GM-CSF的培养基中表现为加速生长(Lange,B.等,血液70:192,1987;Valtieri M.等,免疫学杂志138:4042,1987)。AML 193细胞能在人IL-3存在下增殖也有文献报道(Santoli,D.等,免疫学杂志139:348,1987)。使用细胞系的变异细胞AML 1931.3,该细胞通过洗去生长因子,饥饿细胞因子依赖的AML 193细胞不给生长因子24小时而适应在IL-3中的长期生长。然后这些细胞在含100U/mL IL-3的培养基中,以每孔1×105细胞重新植板在24孔板中。细胞在IL-3中快速生长大约需要2个月。这些细胞通过添加组织培养基(见下)以人IL-3维持,自此后称为AML 1931.3。
用在250×g下离心细胞悬液10分钟,接着移去上清的方法,AML1931.3细胞在冷Hanks平衡盐溶液(HBSS,Gibco,Grand Island,NY)洗6次。沉淀的细胞重悬在HBSS中,重复该程序直到完成6次清洗循环。用该程序洗6次的细胞重悬在组织培养基中,细胞浓度范围为2×105~5×105活细胞/mL。通过Iscove′s修改的Dulbecco′s培养基(IMDM,Hazelton,Lenexa,KS)添加白蛋白、转铁蛋白、脂质和2-巯基乙醇制备这种培养基。加牛白蛋白(Boehringer-Mannheim,Indianapolis,IN)为500μg/mL,加人转铁蛋白(Boehringer-Mannheim,Indianapolis,IN)为100μg/mL;加大豆脂质(Boehringer-Mannheim,Indianapolis,IN)为50μg/mL;以及加2-巯基乙醇(西格玛,圣路易斯,MO)为5×105M。
在96孔Costar 3596组织培养板中,用如上所述添加的组织培养基,以一式三份地进行人白介素-3或多功能性造血受体激动剂蛋白的系列稀释。如果系列稀释完成后,每孔含50μl含有白介素-3或多功能性造血受体激动剂蛋白的培养基。对照板只含组织培养基(阴性对照)。按上述方法制备的AML 1931.3细胞悬液加到每孔中,用吸头吸取50μl(2.5×104细胞)到每孔中。组织培养板在有5%CO2湿润的空气中37℃培养3天。第3天,加在50μl组织培养基中的0.5μCi 3H-胸腺嘧啶(2Ci/mM,New England Nuclear,Boston,MA)。培养物在有5%CO2的湿润空气中,37℃培养18~24小时。用TOMTEC细胞收获仪(TOMTEC,Orange,CT)把细胞DNA收到玻璃滤膜垫上(Pharmacia LKB,Gaithersburg,MD),该细胞收获仪利用一次水洗循环,接着一次70%乙醇循环工作。使滤膜垫空气干燥,然后放入样品袋中,往样品袋加闪烁液(Scintiverse II,Fisher Scienfific,St.Louis,MO或Betaqlate闪烁液,Pharmacia LKB,Gaithersburg,MD)。来自各个组织培养孔的样品的β发射在LKB BetaPlate型号1205的闪烁计数仪(Pharmacia LKB,Gaithersburg,MD)中计数,数据以每分钟掺入每个组织培养孔中的细胞的3H-胸腺嘧啶计数表示。靠测定由梯度浓度的白介素-3或多功能性造血受体激动剂诱导细胞增殖(3H-胸腺嘧啶掺入)定量每种人白介素-3制备物或多功能性造血受体激动剂蛋白制备物的活性。从代表性来说,在这些测定中的定量浓度范围为0.05pM~105pM。活性可由测定提供50%的最大增殖率的白介素-3或多功能性造血受体激动剂蛋白的剂量确定(EC50=0.5×(在所测的所有浓度白介素-3的三重复培养物中,每分钟3H-胸腺嘧啶掺入每孔的最大平均计数值-在缺白介素-3的三重复培养物中观察到的通过3H-胸腺嘧啶掺入测定的本底增殖值)。该EC50值也与1单位的生物活性等价。进行每次测定以原白介素-3作参考标准,结果能确定相对活性水平。
从代表性来说,以系列的2倍稀释液滴定,检测的多功能性造血受体激动剂蛋白的浓度范围为2000pM~0.06pM。
由给出50%最大反应的浓度,用四参数逻辑模型拟合这些数据而确定每个样品的活性。可观察到样品的上部平高线(最大反应)和标准比较没有差别。因此,每个样品的相对效力计算可由样品和如上所示的标准的EC50估计值确定。AML 193.1.3细胞对hIL-3、hGM-CSF和hG-CSF应答而增殖。因此对某些样品进行下列另外测定,以说明多功能性造血受体激动剂蛋白的G-CSF受体激动剂部分有活性。增殖测定用多功能性造血受体激动剂加和减去中和对hIL-3受体激动剂部分的单克隆抗体进行。此外,有Xa因子裂解位点的融合分子被裂解然后纯化,分子的半部分作增殖活性测定。这些实验表明多功能性造血受体激动剂蛋白的2个组分均有活性。
TF1 c-mpl配体依赖的增殖测定
c-mpl配体增殖活性用多能人细胞系TF1的亚克隆测定(Kitamura等,细胞生理学杂志140:323-334[1989])。TF1细胞维持在h-IL3(100U/mL)中。为建立对c-mpl配体应答的亚克隆,细胞维持在传代培养基中,该传代培养基含来自用表达c-mpl配体(pMON 26448)1-153形式的基因转染的BHK细胞的10%上清。大部分细胞死亡,但细胞的亚群存活下来。稀释克隆后,选出c-mpl配体应答克隆,在准备测定之前,这些细胞以每天0.3×106细胞/mL的密度分散在传代培养基中。用于这些细胞的传代培养基如下:RPMI 1640(Gibco),10%FBS(Harlan,Lot#91206)、来自转染BHK细胞的10%c-mpl配体上清、1mM丙酮酸钠(Gibco)、2mM谷氨酰胺(Gibco)和100μg/mL青霉素-链霉素(Gibco)。次日,收获细胞在RPMI或IMDM培养基中洗二次,最后在ATL或测定培养基中洗一次。ATL培养基包括下列成分:IMDM(Gibco)、500μg/mL牛血清白蛋白、100μg/mL人转铁蛋白、50μg/mL大豆脂质、4×10~8Mβ-巯基乙醇以及每1000mL的ATL 2mL的A9909(西格玛、抗生素溶液)。细胞用测定培养基在96孔低蒸发板(Costar)中稀释成0.25×106细胞/mL的终密度,终体积为50μl。以重复样品50μl的体积,50%终浓度加来自转染克隆的瞬时上清(条件培养基),稀释3倍最后稀释成1.8%。阳性对照包括IL-3变异体pMON 13288剂量曲线的三重复样品,最初pMON 13288为1ng/mL,用三倍稀释液稀释成0.0014ng/mL。板在5%CO2 37℃下培养。培养到第6天时,以含0.5Ci3H/孔(NEN)体积为20μl/孔加入板中,让板在5%CO2、37℃培养4小时。收集实验板,在β-plate计数仪上计数。
以其他体外细胞为基础的增殖测定
依据包含分子的因子,按在AML 193.1.3细胞增殖测定相似的方式,本领域的技术人员熟知以其他体外细胞为基础的测定,可用于确定多功能性造血受体激动剂的活性。下列是其他有用的测定法实施例。
TF1增殖测定:TF1是对hIL-3应答的多能人细胞系(Kitamura等,细胞生理学杂志140:323-324[1989])。
32D增殖测定:32D是依赖于鼠IL-3的细胞系,它对人IL-3不产生应答,但对没有物种限制的人G-CSF产生应答。
Baf/3增殖测定:Baf/3是依赖于鼠IL-3的细胞系,它对人IL-3或人c-mpl配体不应答,但对没有物种限制的人G-CSF应答。
T1165增殖测定:T1165细胞是依赖IL-6的鼠细胞系(Nordan等,1986),对IL-6和IL-11应答。
人质膜凝块meg-CSF测定:用于分析巨核细胞集落形成活性(Mazur等,1981)。
转染的细胞系:
如鼠Baf/3细胞系的细胞系能用细胞系不含有的集落刺激因子受体转染,例如人G-CSF受体或人c-mpl受体。针对配体转染受体进入细胞系中,这些转染细胞系就能用于确定配体的活性。
一种上述转染的Baf/3细胞系通过克隆编码c-mpl的cDNA产生,该cDNA来自构成于c-mpl应答细胞系,克隆到质粒pcDNA3(Invitrogen,圣地亚哥,Ca)的多克隆位点上的文库。Baf/3细胞用电穿孔法被质粒转染。在存在鼠IL-3,Wehi条件培养基中,细胞在G418选择下生长。经过有限稀释建立克隆。
应用相似的方法,人G-CSF受体能转染到Baf/3细胞系中,用于确定多功能性造血受体激动剂活性。
c-mpl配体增殖活性分析
方法
1.骨髓增殖测定
a.CD 34+细胞纯化:
告知同意后,骨髓抽取液(15-20mL)从正常同种骨髓供体中获得。细胞在磷酸缓冲盐液(PBS,Gibco-BRL)中1∶3稀释,以30mL铺展在15mL的Histopaque-1077(西格玛)上,然后以300 RCF离心30分钟。收集单核中间界面层,用PBS清洗。用亲和柱按厂家的说明(CellPro,Inc,Bothell WA),从单核细胞制备物中富集CD 34+细胞。富集后,用连接荧光素的抗CD 34单克隆抗体和连接藻红蛋白的抗-CD 38抗体(Becton Dickinson,San Jose CA),流式细胞术分析确定CD 34+细胞的纯度平均为70%。
细胞以40,000细胞/mL重悬在X-Vivo 10培养基(Bio-Whittaker,Walkersville,MD)中,1mL植板在12孔组织培养板(Costar)中。加生长因子rhIL-3为100ng/mL,对某些细胞加(pMON5873)。hIL-3变异因子以10ng/mL~100ng/mL使用。由加100μl上清到1mL培养液中(约10%稀释),测定来自转染有编码c-mpl配体或多功能性造血受体激动剂的BHK细胞的条件培养基。细胞在5%CO2,37℃湿润培养箱中,37℃下培养8-14天。
b.细胞收获和分析:
在培养周期结束时获得每种条件的总细胞计数。作荧光分析和倍性测定,细胞用巨核细胞缓冲液(MK缓冲液:13.6mM柠檬酸钠,1mM1,3二甲基黄嘌呤、2.2μm PGE1、11mM葡萄糖、3%w/v BSA,用PBS溶解pH7.4)(Tomer等,血液70:1735-1742,1987)中清洗,重悬在500μl含抗-CD41a FITC抗体(1∶200,AMAC,Westbrook,ME)的MK缓冲液中,然后用MK缓冲液清洗。作DNA分析,细胞在含0.5%吐温20(Fisher,Fair Lawn NJ)的MK缓冲液中渗透20分钟。在冰上用0.5%吐温20和1%多聚甲醛(Fisher化学公司)固定30分钟,接着用含RNA酶(400U/mL)及碘化丙锭(Calbiochem,LaJolla Ca)(50μg/mL)在冰上温育1-2小时。细胞在FACScan或Vantage流式细胞仪(Becton Dickinson,San Jose,CA)上分析。沿直线收集绿色荧光(CD41a-FITC),红色荧光(PI)的对数信号确定DNA倍性。收集所有细胞,测定属CD 41+细胞的百分数。数据分析用LYSIS(Becton Dickinson,San Jose,CA)软件进行。根据流式细胞术分析(百分数)获得表达CD 41抗原的细胞的百分数。CD 41+细胞/mL的绝对(Abs)数量按:(Abs)=(细胞计数)*(百分数)/100计算。
2.巨核细胞纤维蛋白凝块测定
按上述方法分离富集CD 34+的群体。细胞以25,000细胞/mL悬浮在加或不加细胞因子的培养基中,该培养基由基础Iscoves IMDM培养基添加0.3%BSA、0.4%mg/mL表转铁蛋白、6.67μM FeCl2、25μg/mLCaCl2、25μg/mL L-天冬酰胺、500μg/mL ε-氨基-n-己酸和青霉素/链霉素组成。植到35mm板中前,加凝血酶(0.25单位/mL)以起始凝块形成。细胞在5%CO2、37℃湿润培养箱中,37℃培养13天。
培养周期结束时,板用甲醇∶丙酮(1∶3)固定,空气干燥,直到染色时贮存在-200℃。用过氧化酶免疫细胞化学染色方法(Zymed,Histostain-SP。San Franscisco,CA),使用由抗CD 41a、CD 42和CD 61组成的第一单克隆抗体混合物。染色后统计集落,集落分为阴性、CFU-MK(小集落,1-2集落点和细胞约少于25个)、BFU-MK(多于25个细胞,大和多集落点集落)或混合集落(阳性和阴性细胞的混合物)。
甲基纤维素测定
该测定反映体外集落刺激因子刺激骨髓细胞产生不同类型的造血集落的能力(Bradley等,Aust.Exp Biol.Sci.44:287-300,1966),Pluznik等,J.Cell Comp.Physio 66:319-324,1965)。
方法
大约30mL新鲜、正常、健康的骨髓抽取液从告知同意后的个体中获得。在无菌条件下,样品在50mL圆锥管(#25339-50 Corning,Corning MD)中,用1×PBS(#14040.059生命技术公司,Gaithersburg,MD)溶液1∶5稀释。Ficoll(Histopaque 1077西格玛H-8889)铺层在稀释样品下,用300×g离心30分钟。移取单核细胞带,用1×PBS洗2次和1%BSA PBS(CellPro Co.,Bothel,WA)洗一次。计数单核细胞,用Ceprate LC(CD34)试剂盒(CellPro Co.,Bothel,WA)柱选出CD 34+细胞。进行这步分离是因为在骨髓中的所有干细胞和祖细胞显示CD 34表面抗原。
在35×10mm petri皿(Nunc#174926)中,终体积1.0mL一式三份建立培养物。培养基购自Terry Fox labs(HCC-4230培养基)(Terry Fox Labs,Vancouver,B.C.,加拿大),加红细胞生成素(Amgen,Thousand Oaks,CA.)到培养基中。每皿加3,000~10,000个CD 34+细胞。重组IL-3和多功能性造血受体激动剂蛋白加至终浓度为0.001nM~10nM。重组IL-3从哺乳动物细胞或大肠杆菌中纯化;多功能性造血受体激动剂蛋白在来自转染哺乳动物细胞的条件培养基中,或者从来自转染哺乳动物细胞或大肠杆菌的条件培养基中纯化。由本机构自己提供重组hIL-3、GM-CSF、c-mpl配体和多功能性造血受体激动剂。G-CSF(Neupogen)来自Amgen(Thousand OaksCalf.)。用3cc注射器重新悬浮培养物,每皿分加1.0mL。对照(基线应答)培养没有集落刺激因子。阳性对照培养物加条件培养基(PHA激活的人细胞:Terry Fox Lab.H2400)。培养物温育在37℃、5%CO2湿润空气中。到高峰应答日(第10-11天),用带40×组合物镜的Nikon倒置相差显微镜,统计确定多于50个细胞的造血集落。含有少于50个细胞的细胞群称为簇。可供选择的方法是把集落分散在载玻片上,染色;或者挑取集落,重新悬浮,甩到细胞甩片的载玻片上染色,也能鉴别集落。
人脐带血造血生长因子测定
按惯例来说,骨髓细胞用于体外测定造血集落刺激因子(CSF)的活性。然而,人骨髓并不总是容易得到,而且得考虑供体之间的变异性。脐带血可与骨髓相比拟,作为造血干细胞和祖细胞的一个来源(Broxmeyer等,美国国家科学院院报89:4109-113,1992;Mayani等,血液81:3252-3258,1993)。与骨髓相比,脐带血作为常规的主要成分更容易得到。这也有可能通过混和得自几个供体的新鲜细胞而减少测定的变异性,或者为本目的建一个冷冻保存细胞库。经过修改培养条件,和/或分析谱系特异标志,有可能特异地测定粒细胞/巨噬细胞集落(CFU-GM)、巨核细胞CSF活性或高增殖潜能集落形成细胞(HPP-CFC)活性。
方法
用标准密度梯度液(1.077g/mL Histopaque),从脐带血中24小时内收集分离单核细胞(MNC)。用几种方法,脐带血MNC被进一步作干细胞和祖细胞富集。这些方法包括免疫磁性法选择CD14-、CD34+细胞,用来自应用免疫科学公司(Santa Clara,CA)的包被盒遴选SBA-、CD34+部分。用CellPro(Bothell,WA)亲和素柱选择CD 34+。新鲜分离或冷冻保存的CD 34+细胞富集部分用于测定。制备每种样品系列稀释(浓度范围1pM~1204pM)的重复培养,用1×104细胞在1ml0.9%甲基纤维素含培养基的液中,没有另外的生长因子(MethocultH4230来自干细胞技术公司,Vancouver,BC.)。在一些实验中,用含红细胞生成素(EPO)的Methocult H4330代替Methocult H4230,或者加干细胞因子(SCF)50ng/mL(生物资源国际公司,Camarillo,CA)。培养7-9天后,计数含多于30个细胞的集落。为了排除计数时的主观偏差,测定时盲法计数。
关于用于产生变异体,在细菌、哺乳动物细胞或昆虫细胞中表达重组DNA的重组DNA方法;纯化和重新折叠所需蛋白的方法,以及测定蛋白的生物活性的测定法的另外细节可在共同申请的专利WO 95/00646、WO 94/12639、WO 94/12638、WO 95/20976、WO 95/21197、WO 95/20977、WO 95/21254和US 08/383,035中找到,这些专利作为一个整体在此仅列入参考。
本领域的技术人员熟知的进一步细节可在T.Maniatis等,分子克隆,实验手册,冷泉港实验室,1982)中找到,在该书中引用了参考文献,在此引入仅作参考;也可在J.Sambrook等,分子克隆,实验手册,第二版,冷泉港实验室,1989)中找到,该书引用了参考文献,在此引入仅作参考。
表1
寡核苷酸c-mplNcoI
ACGTCCATGGCNTCNCCNGCNCCNCCTGCTTGTGCACTCCGAGTC
(SEQ ID NO:13)N=A,C,G或TEcompl ATGCACGAATTCCCTGACGCAGAGGGTGGA
(SEQ ID NO:14)c-mplHindIII TGACAAGCTTACCTGACGCAGAGGGTGGACCCT
(SEQ ID NO:15)4L-5′ AATTCGGCAA(SEQ ID NO:16)4L-3′ CATGTTGCCG(SEQ ID NO:17)5L-5′ AATTCGGCGGCAA(SEQ ID NO:18)5L-3′ CATGTTGCCGCCG(SEQ ID NO:19)8L-5′ AATTCGGCGGCAACGGCGGCAA(SEQ ID NO:20)8L-3′ CATGTTGCCGCCGTTGCCGCCG(SEQ ID NO:21)31-5′ CGATCCATGGAGGTTCACCCTTTGCCT(SEQ ID NO:22)31-3′ GATCAAGCTTATGGGCACTGGCTCAGTCT(SEQ ID NO:23)35-5 CGATACATGTTGCCTACACCTGTCCTG(SEQ ID NO:24)35-3′ GATCAAGCTTAAGGGTGAACCTCTGGGCA(SEQ ID NO:25)39-5′ CGATCCATGGTCCTGCTGCCTGCTGTG(SEQ ID NO:26)39-3′ GATCAAGCTTAAGGTGTAGGCAAAGGGTG(SEQ ID NO:27)43-5′ CGATCCATGGCTGTGGACTTTAGCTTGGGA
(SEQ ID NO:28)43-3′ GATCAAGCTTAAGGCAGCAGGACAGGTGT(SEQ ID NO:29)45-5′ CGATCCATGGACTTTAGCTTGGGAGAA(SEQ ID NO:30)45-3′ GATCAAGCTTACACAGCAGGCAGCAGGAC(SEQ ID NO:31)49-5′ CGATCCATGGGAGAATGGAAAACCCAG(SEQ ID NO:32)49-3′ GATCAAGCTTACAAGCTAAAGTCCACAGC(SEQ ID NO:33)82-5′ CGATCCATGGGACCCACTTGCCTCTCA(SEQ ID NO:34)82-3′ GATCAAGCTTACAGTTGTCCCCGTGCTGC(SEQ ID NO:35)109-5′ CAGTCCATGGGAACCCAGCTTCCTCCA(SEQ ID NO:36)109-3′ GATCAAGCTTAAAGGAGGCTCTGCAGGGC(SEQ ID NO:37)116-5′ CGATCCATGGGCAGGACCACAGCTCAC(SEQ ID NO:38)116-3′ GATCAAGCTTACTGTGGAGGAAGCTGGGTT
(SEQ ID NO:39)120-5′ CGATCCATGGCTCACAAGGATCCCAATGCC
(SEQ ID NO:40)120-3′ GATCAAGCTTATGTGGTCCTGCCCTGTGG(SEQ ID NO:41)123-5′ CGATCCATGGATCCCAATGCCATCTTCCTG
(SEQ ID NO:42)123-3′ GATCAAGCTTACTTGTGAGCTGTGGTCCT(SEQ ID NO:43)126-5′ CGATCCATGGCCATCTTCCTGAGCTTCCAA
(SEQ ID NO:44)126-3′ GATCAAGCTTAATTGGGATCCTTGTGAGCTGT
(SEQ ID NO:45)SYNNOXA1.REQ AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA
GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC
TCC(SEQ ID NO:46)SYNNOXA2.REQ CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG
CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA
CGG(SEQ ID NO:47)Llsyn.for GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT
CTAACTGCTC TATAATGAT (SEQ ID NO:48)Llsyn.rev CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC
CTGCGCTTGC TCAAGG(SEQ ID NO:49)L3syn.for GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT
CTGGCGGTGG CAGCGGCGGC GGTTCTAACT GCTCTATAAT
GAT(SEQ ID NO:50)L3syn.rev CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC
GCCAGAGCCA CCACCCTGTT GTTCCTGCGC TTGCTCAAGG
(SEQ ID NO:51)35start.seq GATCGACCAT GGCTCTGGAC CCGAACAACC TC
(SEQ ID NO:52)34rev.seq CTCGATTACG TACAAAGGTG CAGGTGGT
(SEQ ID NO:53)70start.seq GATCGACCAT GGCTAATGCA TCAGGTATTG AG
(SEQ ID NO:54)69rev.seq CTCGATTACG TATTCTAAGT TCTTGACA
(SEQ ID NO:55)91start.seq GATCGACCAT GGCTGCACCC TCTCGACATC CA
(SEQ ID NO:56)90rev.seq CTCGATTACG TAGGCCGTGG CAGAGGGC
(SEQ ID NO:57)101start.seq GATCGACCAT GGCTGCAGGT GACTGGCAAG AA
(SEQ ID NO:58)100rev.seq CTCGATTACG TACTTGATGA TGATTGGA
(SEQ ID NO:59)L-11start.seq GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG
CTGCGCAAGG TGGCGTAGAA CGCG (SEQ ID NO:60)L-11stop.seq CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG
AGCTTCCTGC TCAAGTCTTT AGAG(SEQ ID NO:61)P-blstart.seq GGGCTGCGCA AGGTGGCG (SEQ ID NO:62)P-blstop.seq ACACCATTGG GCCCTGCCAG C(SEQ ID NO:63)39start.seq GATCGACCAT GGCTTACAAG CTGTGCCACC CC
(SEQ ID NO:64)38stop. Seq CGATCGAAGC TTATTAGGTG GCACACAGCT TCTCCT
(SEQ ID NO:65)97start.seq GATCGACCAT GGCTCCCGAG TTGGGTCCCA CC
(SEQ ID NO:66)96stop. Seq CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT
(SEQ ID NO:67)126start.seq GATCGACCAT GGCTATGGCC CCTGCCCTGC AG
(SEQ ID NO:68)125stop. Seq CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT
(SEQ ID NO:69)133start.seq GATCGACCAT GGCTACGCAG GGTGCCATGC CG
(SEQ ID NO:70)132stop.seq CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA
(SEQ ID NO:71)142start.seq GATCGACCAT GGCTTCTGCT TTCCAGCGCC GG
(SEQ ID NO:72)141stop. Seq CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC
(SEQ ID NO:73)GLYXA1 GTAGAGGGCG GTGGAGGCTC C(SEQ ID NO:74)GLYXA2 CCGGGGAGCC TCCACCGCCC TCTAC(SEQ ID NO:75)1GGGSfor TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT
GTCTACACCA TTG(SEQ ID NO:76)1GGGSrev CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA
AGGTGGCGTA GAA(SEQ ID NO:77)Synnoxa1.req AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA
GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC
TCC(SEQ ID NO:240)Synnoxa2.req CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG
CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA
CGG(SEQ ID NO:241)
表2
基因序列pMON30304GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGT(SEQ ID NO:78)pMON26458TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC(SEQ ID NO:79)pMON28548TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:80)pMON28500TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:81)pMON28501TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCGGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:82)pMON28502TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:83)Syntan1
1 CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA51 GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC101 TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT151 AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC201 GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT251 CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC301 GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT351 CTAACTGCTC TATAATGATC GATGAAATTA TACATCACTT AAAGAGACCA401 CCTGCACCTT TGCTGGACCC GAACAACCTC AATGACGAAG ACGTCTCTAT451 CCTGATGGAC CGAAACCTTC GACTTCCAAA CCTGGAGAGC TTCGTAAGGG501 CTGTCAAGAA CTTAGAAAAT GCATCAGGTA TTGAGGCAAT TCTTCGTAAT551 CTCCAACCAT GTCTGCCCTC TGCCACGGCC GCACCCTCTC GACATCCAAT601 CATCATCAAG GCAGGTGACT GGCAAGAATT CCGGGAAAAA CTGACGTTCT651 ATCTGGTTAC CCTTGAGCAA GCGCAGGAAC AACAGTAC
(SEQ ID NO:84)Syntan3
1 CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA51 GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC101 TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT151 AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC201 GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT251 CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC301 GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT351 CTGGCGGTGG CAGCGGCGGC GGTTCTAACT GCTCTATAAT GATCGATGAA401 ATTATACATC ACTTAAAGAG ACCACCTGCA CCTTTGCTGG ACCCGAACAA451 CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC CTTCGACTTC501 CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA551 GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC601 GGCCGCACCC TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG651 AATTCCGGGA AAAACTGACG TTCTATCTGG TTACCCTTGA GCAAGCGCAG701 GAACAACAGT AC(SEQ ID NO:85)pMON31104
1 ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT51 GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA101 AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA151 CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT201 CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG251 TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT301 ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT351 GTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG 501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:86)pMON31105
1 ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG51 TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG101 CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC151 CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTAACT GCTCTATAAT201 GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA CCTTTGCTGG251 ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC301 CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA351 ATACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:87)pMON31106
1 ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA51 AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC101 AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CGATGAAATT151 ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT201 CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA251 ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT301 ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC351 CTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC 701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:88)pMON31107
1 ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT51 GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTAACTGCT101 CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT151 TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA201 CCGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA251 ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA301 TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA351 GTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:89)pMON31108
1 ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT51 GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA101 AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA151 CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT201 CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG251 TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TGGCGGTGGC301 AGCGGCGGCG GTTCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA351 CTTAAAGAGA CCACCTGCAC CTTTGTACGT AGAGGGCGGT GGAGGCTCCC401 CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC501 CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC551 ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG601 CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT651 AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC701 TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA751 CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC801 CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT851 ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 901 ACCTTGGACA CACTGCAGGT GGACGTCGCC GACTTTGCCA CCACCATCTG951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA
(SEQ ID NO:90)pMON31109
1 ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG51 TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG101 CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC151 CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTGGCG GTGGCAGCGG201 CGGCGGTTCT AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA251 AGAGACCACC TGCACCTTTG CTGGACCCGA ACAACCTCAA TGACGAAGAC301 GTCTCTATCC TGATGGACCG AAACCTTCGA CTTCCAAACC TGGAGAGCTT351 CGTAAGGGCT GTCAAGAACT TAGAATACGT AGAGGGCGGT GGAGGCTCCC401 CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC501 CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC551 ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG601 CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT651 AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC701 TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA751 CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC801 CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT851 ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC901 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA
(SEQ ID NO:91)pMON31110
1 ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA51 AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC101 AGGAACAACA GGGTGGTGGC TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC151 TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC201 ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA251 TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC301 AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA351 ACCATGTCTG CCCTCTGCCA CGGCCTACGT AGAGGGCGGT GGAGGCTCCC401 CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC501 CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC551 ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG601 CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT651 AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC701 TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA751 CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC801 CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT851 ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC901 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA
(SEQ ID NO:92)pMON31111
1 ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT51 GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTGGCGGTG101 GCAGCGGCGG CGGTTCTAAC TGCTCTATAA TGATCGATGA AATTATACAT151 CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA201 CGAAGACGTC TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG251 AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG301 GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC351 CTCTCGACAT CCAATCATCA TCAAGTACGT AGAGGGCGGT GGAGGCTCCC401 CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC501 CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC551 ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG601 CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT651 AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC701 TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA751 CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC801 CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT851 ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC901 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA
(SEQ ID NO:93)pMON131821 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC801 GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG CTCAAGTCTT851 TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG901 CTGTGTGCCA CCTAATAA(SEQ ID NO:94)pMON13183
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC851 CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG901 CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG951 TGCCACCTAA TAA(SEQ ID NO:95)pMON13184
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC401 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT451 GCCACCACCA TCTGGCAGGA GATGGAAGAA CTGGGAATGG CCCCTGCCCT501 GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC551 GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG601 TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG651 CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG701 GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC751 CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC801 TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA851 GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG901 GAAGGGATAT CCTAATAA(SEQ ID NO:96)pMON13185
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTGTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA651 CCGCGTTCTA CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC701 AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT751 GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC801 CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC851 TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA901 CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG951 GATATCCTAA TAA(SEQ ID NO:97)pMON13186
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT451 GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG501 CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCTCTG551 GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG601 AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC651 CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG701 GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG751 GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT801 CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA851 CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG901 GAAGAACTGG GATAATAA(SEQ ID NO:98)pMON13187
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC601 TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA 651 GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA701 AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC751 CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG801 CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC851 AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG901 CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA951 ACTGGGATAA TAA(SEQ ID NO:99)pMON13188
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA451 GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG501 CGTTCTACGC CACCTTGCGC AGCCCTCTGG CGGCTCTGGC GGCTCTCAGA551 GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GGGCGATGGC601 GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA651 GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA701 GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC751 CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT801 ATCCCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG851 ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT901 GCCCTGCAGC CCTAATAA(SEQ ID NO:100)pMON13189
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT 901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT951 GCAGCCCTAA TAA(SEQ ID NO:101)pMON13190
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG451 AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTC501 TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG551 TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC601 ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT651 GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC701 TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG751 CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA801 CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA851 TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG901 CCGGCCTTCG CCTAATAA(SEQ ID NO:102)pMON13191
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTCTGCT451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG551 GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA601 AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA651 CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA701 TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA751 GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT801 GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC851 TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA901 GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC951 CTTCGCCTAA TAA(SEQ ID NO:103)pMON13192 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC801 GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC851 TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC901 CAGGAGAAGC TGTGTGCCAC CTAATAA(SEQ ID NO:104)pMON13193
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC851 CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG901 TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA951 GAAGCTGTGT GCCACCTAAT AA(SEQ ID NO:105)pMON25190
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC401 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT451 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT501 GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC551 GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG601 TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT TGGGCCCTGC651 CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA701 AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC751 AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT801 CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG851 GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG901 CAGGCCCTGG AAGGGATATC CTAATAA(SEQ ID NO:106)pMON25191
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG451 TTGGCTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA651 CCGCGTTCTA CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT701 CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT TAGAGCAAGT GAGAAAGATC751 CAGGGCGATG GCGCAGCGCT CCAGGAGAAG CTGTGTGCCA CCTACAAGCT801 GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG GGCATCCCCT851 GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC901 TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC951 CCTGGAAGGG ATATCCTAAT AA(SEQ ID NO:107)pMON13194
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT 451 GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG501 CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCACAC551 CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA601 GAGCAAGTGA GAAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT651 GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC701 ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC751 CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA801 CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA851 CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG901 CAGCAGATGG AAGAACTGGG ATAATAA(SEQ ID NO:108)pMON13195
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CACACCATTG601 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA651 AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA951 GATGGAAGAA CTGGGATAAT AA(SEQ ID NO:109)pMON13196
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA451 GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG501 CGTTCTACGC CACCTTGCGC AGCCCACACC ATTGGGCCCT GCCAGCTCCC551 TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AAAGATCCAG601 GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG651 CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG 701 CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG751 AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT801 GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG851 ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA901 ATGGCCCCTG CCCTGCAGCC CTAATAA(SEQ ID NO:110)pMON13197
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC751 CTGACCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC951 CCCTGCCCTG CAGCCCTAAT AA(SEQ ID NO:111)pMON13198
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG451 AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCAC501 ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT551 TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG601 CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG651 ACACTCTCTG GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG701 CCCTGCAGCT GGCAGGCTGC TTGAGCCAAC TCCATAGCGG CCTTTTCCTC751 TACCAGGGGC TCCTGCAGGC CCTGGAAGGG ATATCCCCCG AGTTGGGTCC801 CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC ACCACCATCT851 GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG901 GGTGCCATGC CGGCCTTCGC CTAATAA(SEQ ID NO:112)pMON13199
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTCTGCT451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT551 TGGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG601 CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG651 TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT701 CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG751 CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA801 GGGGCTCCTG CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT851 TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CATCTGGCAG901 CAGATGGAAG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC951 CATGCCGGCC TTCGCCTAAT AA(SEQ ID NO:113)pMON31112
1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC251 CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT951 GCAGCCCTAA TAA(SEQ ID NO:114)pMON31113
1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG 101 ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC251 CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC951 CCCTGCCCTG CAGCCCTAAT AA(SEQ ID NO:115)pMON31114
1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC251 CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT951 GCAGCCCTAA TAA(SEQ ID NO:116)pMON31115
1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC251 CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC951 CCCTGCCCTG CAGCCCTAAT AA(SEQ ID NO:117)pMON28505GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA (SEQ ID NO:118)pMON28506GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT(SEQ ID NO:119)pMON28507GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT(SEQ ID NO:120)pMON28508GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT(SEQ ID NO:121)pMON28509GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG(SEQ ID NO:122)pMON28510GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAACTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGACCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGTTG(SEQ ID NO:123)pMON28511GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG(SEQ ID NO:124)pMON28512GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT(SEQ ID NO:125)pMON28513GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG(SEQ ID NO:126)pMON28514GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA(SEQ ID NO:127)pMON28515GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:128)pMON28516GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT(SEQ ID NO:129)pMON28519GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA(SEQ ID NO:130)pMON28520GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT(SEQ ID NO:131)pMON28521GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTA~CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT(SEQ ID NO:132)pMON28522GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTCCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT(SEQ ID NO:133)pMON28523GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG(SEQ ID NO:134)pMON28524GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG(SEQ ID NO:135)pMON28525GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG(SEQ ID NO:136)pMON28526GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT(SEQ ID NO:137)pMON28527GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG(SEQ ID NO:138)pMON28528GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA(SEQ ID NO:139)pMON28529GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:140)pMON28530GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT(SEQ ID NO:141)pMON28533GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGCATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGTAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA(SEQ ID NO:142)pMON28534GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT(SEQ ID NO:143)pMON28535GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT(SEQ ID NO:144)pMON28536GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT(SEQ ID NO:145)pMON28537GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG(SEQ ID NO:146)pMON28538GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG(SEQ ID NO:147)pMON28539GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG(SEQ ID NO:148)pMON28540GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT(SEQ ID NO:149)pMON28541GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG(SEQ ID NO:150)pMON28542GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA(SEQ ID NO:151)pMON28543GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:152)pMON28544GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT(SEQ ID NO:153)pMON28545GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:154)pMON15981
1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTACAAG451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC851 CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG901 CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG951 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA;
(SEQ ID NO:155)pMON159821 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTCCCGAG451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA651 CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA701 CACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT751 TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA801 GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG851 GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG901 GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT951 CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCTAA TAA;
(SEQ ID NO:156)pMON159651 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTCTGCT451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCGGCGGCG551 GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC601 TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC651 AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG701 AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC751 TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA801 TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT851 CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC901 TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC951 CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTAA TAA
(SEQ ID NO:157)pMON159661 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTATGGCC451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CGGCGGCGGC601 TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT651 CCTGCTCAAG TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG701 CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CCCCGAGGAG751 CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC801 CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA851 GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AGGGATATCC901 CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT951 TGCCACCACC ATCTGGCAGC AGATGGAAGA ACTGGGATAA TAA
(SEQ ID NO:158)pMON159671 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TACACCATTA601 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA651 AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA951 GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA
(SEQ ID NO:159)pMON159601 ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT51 CAAGTCTTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC101 AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTG151 CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC201 CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC251 TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG301 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC351 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC401 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA451 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA501 CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA551 CACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT601 TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA651 GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG701 GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG751 GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT801 CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC851 CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC901 TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA1001 TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT1051 CTACGCCACC TTGCGCAGCC CTGATAA(SEQ ID NO:160)PMON32132TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:249)PMON32133TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:250)pMON32134TCCCGAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG(SEQ ID NO:251)Pmon131811 CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG51 AGACCACCTG CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT101 CTCTATCCTG ATGGATCGAA ACCTTCGACT TCCAAACCTG GAGAGCTTCG151 TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT201 CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA251 TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA301 CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAgag351 ggcggtggag gctcCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA401 CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGTAAGGTA451 CCGCATGCAA GCTT(SEQ ID NO:257)Pmon13180.Seg1 CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG51 AGACCACCTG CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT101 CTCTATCCTG ATGGATCGAA ACCTTCGACT TCCAAACCTG GAGAGCTTCG151 TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT201 CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA251 TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA301 CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAgag351 ggcggtggag gctcCCCGGG TGGTGGTTCT GGCGGCGGCT CCAACATGTA401 AGGTACCGCA TGCAAGCTT(SEQ ID NO:258)
表3
蛋白序列pMON26458pepSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe(SEQ ID NO:161)pMON28548pepSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:162)pMON28500SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:163)pMON28501SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:164)pMON28502SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:165)13182.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Pne Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Pne Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr(SEQ ID NO:166)13183.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr (SEQ ID NO:167)13184.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GiuGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser(SEQ ID NO:168)13185.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile ASn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser(SEQ ID NO:169)13186.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Vai Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProSer Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln LeuHis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu GluGly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln LeuAsp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu GluLeu Gly(SEQ ID NO:170)13187.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProSer Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln LeuHis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu GluGly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln LeuAsp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu GluLeu Gly (SEQ ID NO:171)13188.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly SerGln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile GlnGly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu GlnLeu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu TyrGln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro(SEQ ID NO:172)13189.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu ASn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly SerGln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile GlnGly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu GlnLeu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu TyrGln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro (SEQ ID NO:173)13190.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu AspVal Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro AlaPhe Ala(SEQ ID NO:174)13191.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu AspVal Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro AlaPhe Ala (SEQ ID NO:175)13192. PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr(SEQ ID NO:176)13193.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr (SEQ ID NO:177)25190.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser(SEQ ID NO:178)pMON25191.PepAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser(SEQ ID NO:179)13194.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProThr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu LeuLys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala AlaLeu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro GluGlu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala ProLeu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys LeuSer Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln GlnMet Glu Glu Leu Gly(SEQ ID NO:180)13195.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProThr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu LeuLys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala AlaLeu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro GluGlu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala ProLeu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys LeuSer Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln GlnMet Glu Glu Leu Gly (SEQ ID NO:181)13196.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val ArgLys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys AlaThr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly HisSer Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser GlnAla Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser ProGlu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala AspPhe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met AlaPro Ala Leu Gln Pro (SEQ ID NO:182)13197. PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val ArgLys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys AlaThr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly HisSer Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser GlnAla Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser ProGlu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala AspPhe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met AlaPro Ala Leu Gln Pro (SEQ ID NO:183)13198. PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr LeuGln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln MetGlu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly AlaMet Pro Ala Phe Ala(SEQ ID NO:184)13199.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr LeuGln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln MetGlu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly AlaMet Pro Ala Phe Ala (SEQ ID NO:l85)31104.PepLeu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg AlaVal Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu ArgAsn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser ArgHis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg GluLys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile IleHis His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:186)31105.PepAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile IleLys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe TyrLeu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly SerAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:187)31106.PepAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu LeuAsp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met AspArg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala ValLys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg AsnLeu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:188)31107.PepAla Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr LeuVal Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser AsnCys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg ProPro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp ValSer Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu SerPhe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile GluAla Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:189)31108.PepLeu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg AlaVal Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu ArgAsn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser ArgHis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg GluLys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn CysSer Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro ProAla Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro(SEQ ID NO:190)31109. PepAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile IleLys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe TyrLeu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly SerGly Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu AspPro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp ArgAsn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val LysAsn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro(SEQ ID NO:191)31110. PepAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly GlyGly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro(SEQ ID NO:192)31111.PepAla Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr LeuVal Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser GlyGly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp GluIle Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp ProAsn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg AsnLeu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys AsnLeu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro(SEQ ID NO:193)pMON15981MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThr(SEQ ID NO:194)pMON15982MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer(SEQ ID NO:195)pMON15965MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAla (SEQ ID NO:196)pMON15966MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLauAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGly(SEQ ID NO:197)pMON15967MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:198)pMON31112.pepMetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:199)pMON31113.pepMetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:200)pMON31114.pepMetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:201)pMON31115.pepMetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:202)pMON28505AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro(SEQ ID NO:203)pMON28506AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisPro(SEQ ID NO:204)pMON28507AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro(SEQ ID NO:205)pMON28508AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro(SEQ ID NO:206)pMON28509AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaVal(SEQ ID NO:207)pMON28510AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeu(SEQ ID NO:208)pMON28511AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu(SEQ ID NO:209)pMON28512AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu(SEQ ID NO:210)pMON28513AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln(SEQ ID NO:211)pMON28514AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr(SEQ ID NO:212)pMON28515AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys(SEQ ID NO:213)pMON28516AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsn(SEQ ID NO:214)pMON28519AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro(SEQ ID NO:215)pMON28520AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisPro(SEQ ID NO:216)pMON28521AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro(SEQ ID NO:217)pMON28522AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsrLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro(SEQ ID NO:2l8)pMON28523AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaVal(SEQ ID NO:219)pMON28524AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeu(SEQ ID NO:220)pMON28525AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu(SEQ ID NO:221)pMON28526AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu(SEQ ID NO:222)pMON28527AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln(SEQ ID NO:223)pMON28528AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLauGlyThrGlnLeuProProGlnGlyArgThrThr(SEQ ID NO:224)pMON28529AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys(SEQ ID NO:225)pMON28530AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsn(SEQ ID NO:226)pMON28533AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro(SEQ ID NO:227)pMON28534AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisPro(SEQ ID NO:228)pMON28535AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro(SEQ ID NO:229)pMON28536AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro(SEQ ID NO:230)pMON28537AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaVal(SEQ ID NO:23l)pMON28538AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeu(SEQ ID NO:232)pMON28539AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu(SEQ ID NO:233)pMON28540AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu(SEQ ID NO:234)pMON28541AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln(SEQ ID NO:235)pMON28542AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr(SEQ ID N0:236)pMON28543AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys(SEQ ID NO:237)pMON28544AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsn(SEQ ID NO:238)pMON28545AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLys(SEQ ID NO:239)pMON32132SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:252)PMON32133SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:253)PMON32134SerProAlaPreProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg(SEQ ID NO:254)
下列实施例更为详细地说明本发明,尽管可以理解本发明并不局限于这些具体的实施例。
实施例1
亲本BHK表达载体的构建
A.从哺乳动物表达质粒中移去AflIII位点
构建新的哺乳动物表达载体,以接受NcoI-HindIII或AflIII-HindIII基因片段在框内,其3′端为hIL-3受体激动剂pMON 13146(WO 94/12638)基因和小鼠IgG2b接头片段。首先,单一的AflIII位点从pMON 3934中移去,pMON 3934是pMON 3359的衍生体。pMON3359是基于pUC18,含有哺乳动物表达盒的载体。该盒包括单纯性疱疹病毒启动子IE 110(-800~+120)后续以修饰过的人IL-3信号肽序列和SV40晚期聚腺苷化(poly-A)信号,被亚克隆到pUC18多接头中(见Hippenmeyer等,生物技术,1993,pp.1037-1041)。便于基因产物分泌到细胞外而修饰过的人IL-3信号序列,其侧翼5′端为BamHI位点,3′端为唯一的NcoI位点。唯一的HindIII位点,其3′端向NcoI位点而5′端向poly-A序列。编码信号肽的DNA序列显示见下(限制性酶位点显示如上)。在NcoI位点中的ATG(甲硫氨酸)密码子在框内,具信号肽的起始子ATG(下划线);
BamHI NcoI
5′GGATCCACC
ATGAGCCGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCGCCATGG
(SEQ ID NO:255)
用AflIII消化,然后加DNA聚合酶和核苷酸补齐突出端的方法,从pMON 3934移去单一的AflIII位点。消化的DNA片段经Magic PCR Cleanup试剂盒(Promega)纯化,用T4 DNA连接酶连接。连接反应液转化到DH5αTM中,细胞涂皿于加氨苄青霉素的LB-琼脂上。用AflIII和HindIII限制性分析筛选失去AflIII位点的各个集落,如果AflIII位点被移去,酶切的结果为单一片段。得到的质粒命名为pMON 30275。
B.转移hIL-3受体激动剂pMON l3416/IgG2b盒到pMON 30275中。
来自pMON 30245的NcoI-HindIII片段(大约425bp)连接到pMON30275的NcoI-HindIII片段(大约3800bp)上。pMON 30245(专利号WO 94/12638)含有编码连有小鼠IgG2b铰链片段的hIL-3受体激动剂pMON 13416的基因。AflIII位点3′端紧邻IgG2b铰链片段,其5′端向HindIII位点。作为NcoI-HindIII或AflIII-HindIII片段在框内具有hIL-3变异体pMON 13416/IgG2b铰链,基因能被克隆到AflIII-HindIII位点中,以产生新嵌合片段。NcoI位点和AflIII位点有匹配的突出端,能连接但两个识别位点会失去。这种克隆法的反应产物质粒pMON30304,该质粒含有编码连有小鼠IgG2b铰链区的hIL-3变异体pMON13416(SEQ ID NO:78)的DNA序列。
实施例2
含二聚体模板的c-mpl配体(1-153)基因一个拷贝的中介质粒的构建
为产生具有c-mpl(1-153)配体的编码序列后连有单独的EcoRI限制性位点的质粒DNA,通过反向转录酶/聚合酶链反应(RT/PCR)分离基因。人胎儿(lot#38130)和成人肝(lot#46018)A+RNA从Clontech(Palo Alto,CA)得到,用作c-mpl配体信使RNA(mRNA)的来源。第一链cDNA反应用从InVitrogen(San Diego,CA)获得的cDNA循环TM试剂盒进行。在RT反应中,随机引物和寡dT引物用于从人和胎儿肝mRNA合并物中产生cDNA。为扩增编码1-153氨基酸的c-mpl配体基因片段,RT产物用作PCR的模板,合并使用的引物,正向引物为c-mplNcoI(SEQ ID NO:13)和反向引物为Ecompl。c-mplNcoI引物与c-mpl配体基因退火(碱基#279-311,依据来自基因库登记号#L33410或de Sauvage等,自然369:533-538(1994)的c-mpl配体序列),编码的NcoI限制酶位点其5′端紧接着c-mpl配体的第1个密码子(Ser+1)。NcoI限制性内切酶位点在Ser+1前编码甲硫氨酸和丙氨酸密码子,包括对c-mpl配体的Ala密码子和最先的4个密码子(Ser、Pro、Ala、和Pro)的密码简并性。Ecompl引物与c-mpl配体的碱基#720-737退火,编码EcoRI位点(GAATTC),在框内具有紧接Arg-153之后的c-mpl配体基因。在Arg-153之后,EcoRI位点产生了谷氨酸和苯丙氨酸密码子。大约480bp的PCR产物被纯化,用NcoI和EcoRI消化,然后连接到pMON 3993的NcoI-EcoRI载体片段上(大约4550bp)。pMON 3993是pMON 3359的衍生体(在实施例1所述)。作为BamHI片段亚克隆到位于IE 110启动子和poly-A信号之间单独BamHI位点中的人IL-3信号肽序列,在其3′端含NcoI位点,其后为单独的EcoRI位点。本克隆法的反应产物是pMON 26458质粒,该质粒含有编码c-mpl配体氨基酸1-153(SEQ ID NO:161)的(SEQ ID NO:79)DNA序列。
实施例3
含二聚体模板第2个基因的亲本质粒的构建
为扩增起点在1位氨基酸(Ser)和在153位(Arg)氨基酸之后为终止密码子的c-mpl配体基因,来自实施例2的RT反应液用作PCR模板,合并使用下列引物;c-mplNcoI(SEQ ID NO:13)(正向引物)和c-mplHindIII(SEQ ID NO:15)(反向引物)。c-mplNcoI(SEQ ID NO:13)引物已在实施例2描述。c-mplHindIII(SEQ IDNO:15)引物与c-mpl配体的碱基#716-737退火,在紧接最终密码子,Arg153之后加上终止密码子和HindIII限制性内切酶位点。
从RT cDNA样品中产生两种类型的PCR产物,一种缺失相应于氨基酸112-115位的密码子,而一种没有这些密码子的缺失。c-mpl配体PCR产物(约480bp)用NcoI和HindIII限制性内切酶消化,以转移到哺乳动物表达载体pMON 3934中。pMON 3934用NcoI和HindIII消化(约3800bp),可接受PCR产物。编码c-mpl配体氨基酸1-153(SEQ ID NO:252)的质粒pMON 32132(SEQ ID NO:249)是这种克隆法的反应产物。这种克隆法的反应产物是编码c-mpl配体氨基酸1-153(SEQ ID NO:253)的质粒pMON 32134(SEQ IDNO:250)。质粒pMON 32133(SEQ ID NO:251)也是这种克隆法的反应产物,该质粒编码具有缺乏密码子112-115(Δ112-115)的c-mpl配体氨基酸1-153(SEQ ID NO:254)。
实施例4
在第2个c-mol配体基因中产生具Δ112-115缺失的PCR二聚体
模板5L
构建产生新形式c-mpl配体的PCR模板,和EcoRI/AflIII 5L合成寡核苷酸接头5L-5′(SEQ ID NO:18)和5L-3′(SEQ ID NO:19)一起,通过把3.7 kbp的pMON 26458的BstXI/EcoRI片段连接到来自pMON 32133(含缺失的氨基酸112-115)的1kbp NcoI/BstXI片段上而成。
接头的EcoRI端将连接到pMON 26458的EcoRI端上。接头的AdlIII端将连接到pMON 32133的NcoI位点上,连接后它们的任一限制性位点将不再保留。pMON 26458和pMON 32133的BstXI位点也连接在一起。质粒pMON 28548是本克隆法的反应产物,含有编码经GluPheGlyGlyAsnMetAla(SEQ ID NO:222)接头融合到缺失氨基酸112-115的氨基酸1-153 c-mpl配体(SEQ ID NO:162)的氨基酸c-mpl配体的(SEQ ID NO:80)DNA序列。
实施例5
PCR二聚体模板4L的产生
构建产生新型c-mpl配体的PCR模板,和EcoRI/AflIII 4L合成寡核苷酸接头4L-5′(SEQ ID NO:16)和4L-3′(SEQ ID NO:17)一起,通过把3.7 kbp的pMON 26458 BstXI/EcoRI片段连接到来自pMON32132的1kpb NcoI/BstXI片段。
接头的EcoRI端将连接到pMON 26458的EcoRI端。接头的AflII端将连接到pMON 32132的NcoI位点上,连接后它们的任一个限制性位点将不再保留。pMON 26458和pMON 32132的BstXI位点也连接在一起。质粒pMON 26458是本克隆法的反应产物,含有编码经GluPheGlyAsnMetAla(SEQ ID NO:223)接头(4L)融合到氨基酸1-153 c-mpl配体(SEQ ID NO:163)的氨基酸1-153 c-mpl配体的(SEQ ID NO:82)DNA序列。
实施例6
PCR二聚体模板5L的产生
构建产生c-mpl配体新形式的PCR模板,和EcoRI/AflIII 5L合成寡核苷酸接头5L-5′(SEQ ID NO:18)和5L-3′(SEQ ID NO:19)一起,通过把3.7 kbp的pMON 26458的BstXI/EcoRI片段连接到来自pMON 32132的1kbp NcoI/BstXI片段上而成。
接头的EcoRI端将连接到pMON 26458的EcoRI端上。接头AflIII端将连接到pMON 32132的NcoI位点上,连接后,它们的任一个限制性位点将不再保留。pMON 26458和pMON 32132的BstXI位点也将连接在一起。质粒pMON 28501是本克隆法的反应产物,含有经GluPheGlyGlyAsnMetAla(SEQ ID NO:222)接头(5L)融合到氨基酸1-153 c-mpl配体(SEQ ID NO:164)上的氨基酸1-153 c-mpl配体的(SEQ ID NO: 82)DNA序列。
实施例7
PCR二聚体模板8L的产生
构建产生新型c-mpl配体的PCR模板,和EcoRI/AflIII 8L合成寡核苷酸接头8L-5′(SEQ ID NO:20)和8L-3′(SEQ ID NO:21)一起,通过把pMON 26458的3.7kbp BsxI/EcoRI片段连接到来自pMON32134的1kbp NcoI/BstXI片段而成。
接头的EcoRI端将连接到pMON 26458的EcoRI端上。接头的AflIII端将连接到pMON 32134的NcoI位点上,连接后,它们的任一个限制性位点将不再保留。pMON 26458和pMON 32134的BstXI位点也将连接在一起。质粒pMON 28502是本克隆法的反应产物,含有经GluPheGlyGlyAsnGlyGlyAsnMetAla(SEQ ID NO:224)接头(8L)融合到氨基酸1-153 c-mpl配体(SEQ ID NO:165)上的氨基酸1-153 c-mpl配体的(SEQ ID NO:83)DNA序列。
实施例8-44
具有新N-末端和C-末端的新型c-mpl配体基因的产生
A.通过PCR产生编码新型c-mpl配体受体激动剂的基因。
编码新型c-mpl配体受体激动剂基因用方法III产生(Horlick等,蛋白质工程5:427-433,1992)。PCR反应使用二聚体模板pMONs28500、28501、28502或28548和如下合成引物组的一对之一进行(第一位数指在原始序列中第一个氨基酸的位置。例如,31-5′和31-3′分别指5′和3′端寡核苷酸引物,其序列在密码子上的起点与原始序列31位残基相对应)。
31-5′(SEQ ID NO:22)和31-3′(SEQ ID NO:23),35-5′(SEQ ID NO:24)和35-3′(SEQ ID NO:25),39-5′(SEQ ID NO:26)和39-3′(SEQ ID NO:27),43-5′(SEQID NO:28)和43-3′(SEQ ID NO:29),45-5′(SEQ ID NO:30)和45-3′(SEQ ID NO:31),49-5′(SEQ ID NO:32)和49-3′(SEQ ID NO:33),82-5′(SEQ ID NO:34)和82-3′(SEQ ID NO:35),109-5′(SEQ ID NO:36)和109-3′(SEQ ID NO:37),115-5′(SEQ ID NO:38)和115-3′(SEQID NO:39),120-5′(SEQ ID NO:40)和120-3′(SEQ ID NO:41),123-5′(SEQ ID NO:42)和123-3′(SEQ ID NO:43),126-5′(SEQ ID NO:44)和126-3′(SEQ ID NO:45)。
用于PCR反应的模板和寡核苷酸对如表4所示。产生的产物大约为480bp,通过Magic PCR Clean up试剂盒(Promega)纯化。
B.为产生嵌合体,把新型c-mpl受体激动剂基因产物亚克隆到哺乳动物表达载体中。
c-mpl受体激动剂基因PCR产物用NcoI和HindIII或AflIII和HindIII限制性内切酶(大约470bp)消化,以便转移到哺乳动物表达载体中。表达载体pMON 30304用NcoI和HindIII(大约4200bp)消化,作为NcoI-HindIII或AflIII-HindIII片段而接受PCR产物。 PCR产物的限制性消化和所得到的质粒如表4所示。
表4
PCR 产物 PCR 产物 在c-mpl配体实施例序号PCR 模板 引物组 限制性消化 接头 产生的质粒 中的断裂点
pMON实施例8 pMON28501 31 NcoI/HindIII 5L 28505 30-31实施例9 pMON28501 35 AflIII/HindIII 5L 28506 34-35实施例10 pMON28501 39 NcoI/HindIII 5L 28507 38-39实施例11 pMON28501 43 NcoI/HindIII 5L 28508 42-43实施例12 pMON28501 45 NcoI/HindIII 5L 28509 44-45实施例13 pMON28501 49 NcoI/HindIII 5L 28510 48-49实施例14 pMON28501 82 NcoI/HindIII 5L 28511 81-82实施例15 pMON28501 109 NcoI/HindIII 5L 28512 108-109实施例16 pMON28501 116 NcoI/HindIII 5L 28513 115-116实施例17 pMON28501 120 NcoI/HindIII 5L 28514 119-120实施例18 pMON28501 123 NcoI/HindIII 5L 28515 122-123实施例19 pMON28501 126 NcoI/HindIII 5L 28516 125-126实施例20 pMON28500 31 NcoI/HindIII 4L 28519 30-31实施例21 pMON28500 35 AflIII/HindIII 4L 28520 34-35实施例22 pMON28500 39 NcoI/HindIII 4L 28521 38-39实施例23 pMON28500 43 NccI/HindIII 4L 28522 42-43实施例24 pMON28500 45 NcoI/HindIII 4L 28523 44-45实施例25 pMON28500 49 NcoI/HindIII 4L 29524 48-49实施例26 pMON28500 82 NcoI/HindIII 4L 28525 81-83实施例27 pMON28500 109 NcoI/HindIII 4L 28526 108-109实施例28 pMON28500 116 NcoI/HindIII 4L 28527 115-116实施例29 pMON28500 120 NcoI/HindIII 4L 28528 119-120实施例30 pMON28500 123 NcoI/HindIII 4L 28529 122-123实施例31 pMON28500 126 NcoI/HindIII 4L 28530 125-126实施例32 pMON28502 31 NcoI/HindIII 8L 28533 30-31实施例33 pMON28502 35 AflIII/HindIII 8L 28524 34-35实施例34 pMON28502 39 NcoI/HindIII 8L 28535 38-39实施例35 pMON28502 43 NcoI/HindIII 8L 26536 42-43
表4续
PCR 产物 PCR 产物 在c-mpl配体实施例序号 PCR 模板 引物组 限制性消化 接头 产生的质粒 中的断裂点
pMON实施例36 pM.N28502 45 NcoI/HindIII 8L 28537 44-45实施例37 pMON28502 49 NcoI/HindIII 8L 28538 48-49实施例38 pMON28502 82 NcoI/HindIII 8L 28539 81-82实施例39 pMON28502 109 NcoI/HindIII 8L 28540 108-109实施例40 pMON28502 116 NcoI/HindIII 8L 28541 115-116实施例41 pMON28502 120 NcoI/HindIII 8L 28542 119-120实施例42 pMON28502 123 NcoI/HindIII 8L 28543 122-123实施例43 pMON28502 126 NcoI/HindrII 8L 28544 125-126实施例44 pMON28548 123 NcoI/HindIII 5L 28545 122-123
实施例45
pMON15960的构建
构建中介质粒用于构建含编码具有新N-末端和C-末端的G-CSF Ser17的DNA序列。质粒pACYC 177(Chang,A.C.Y.和Cohen,S.N.细菌学杂志134:1141-1156,1978)的DNA用限制性内切酶HindIII和BamHI消化,结果产生一条3092碱基对的HindIII、BamHI片段。质粒pMON 13037(WO 95/21254)的DNA用BglII和FspI消化,结果产生一条616碱基对的BglII、FspI片段。第二个样品质粒pMON13037的DNA用NcoI和HindIII消化,结果产生一条556碱基对的NcoI、HindIII片段。合成的DNA寡核苷酸1GGGSfor(SEQ ID NO:76)和1GGGSrev(SEQ ID NO:77)相互退火,然后用AflIII和FspI消化,结果产生一条21碱基对的AflIII、FspI片段。连接限制性片段,连接反应混合液用于转化大肠杆菌k-12 JM 101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,用限制性分析证实正确插入。
实施例46
pMON15981的构建
所构建的pMON 15981是一种含编码多功能性造血受体激动剂的DNA序列的质粒。质粒pMON 15960的DNA用限制性内切酶SmaI消化,用作PCR反应的模板,PCR反应的引物用合成的DNA寡核苷酸38终止引物(SEQ ID NO:65)和39起始引物(SEQ ID NO:64),结果扩增出一条576碱基对的DNA片段。扩增片段用限制性内切酶HindIII和NcoI消化,结果产生一条558碱基对的HindIII、NcoI片段。质粒pMON 13181的DNA用HindIII和AflIII消化,结果产生一条4068碱基对的HindIII、AflII片段。连接限制性片段,连接反应混合液用于转化大肠杆菌k-12 JM 101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,用限制性分析及测序以证实正确插入。质粒pMON15981含编码下列氨基酸序列的(SEQ ID NO:155)DNA序列。MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThr(SEQ ID NO:195)
实施例47
pMON 15982的构建
所构建的pMON 15982是一种含有编码多功能性造血受体激动剂的DNA序列的质粒。质粒pMON 15960的DNA用限制性内切酶SmaI消化,用作PCR反应的模板,PCR反应的引物用合成的DNA寡核苷酸96终止引物(SEQ ID NO:67)和97起始引物(SEQ ID NO:66),结果扩增出一条576碱基对的DNA片段。扩增片段用限制性内切酶HindIII和NcoI消化,结果产生一条558碱基对的HindIII、NcoI片段。质粒pMON 13181的DNA用HindIII和AflIII消化,结果产生一条4068碱基对的HindIII、AflIII片段。连接限制性片段,连接反应混合液用于转化大肠杆菌k-12 JM 101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,用限制性分析及测序以证实正确插入。质粒pMON15982含有编码下列氨基酸序列的(SEQ ID NO:157)DNA序列:MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer(SEQ ID NO:196)
实施例48
pMON 15965的构建
所构建的pMON 15965是一种含编码多功能性造血受体激动剂的DNA序列的质粒。质粒pMON 15960的DNA用限制性内切酶SmaI消化,用作PCR反应的模板,PCR反应的引物用合成的DNA寡核苷酸142终止引物(SEQ ID NO:73)和141起始引物(SEQ ID NO:72),结果扩增出一条576碱基对的DNA片段。扩增片段用限制性内切酶HindIII和NcoI消化,结果产生一条558碱基对的HindIII、NcoI片段。质粒pMON 13181的DNA用HindIII和AflII消化,结果产生一条4068碱基对的HindIII、AflIII片段。连接限制性片段,连接反应混合液用于转化大肠杆菌k-12 JM 101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,用限制性分析及测序证实正确插入。质粒pMON15965含有编码下列氨基酸序列的(SEQ ID NO:157)DNA序列:MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAla(SEQ ID NO:196)
实施例49
pMON 15966的构建
所构建的pMON 15966是一种含编码多功能性造血受体激动剂的DNA序列的质粒。质粒pMON 15960的DNA用限制性内切酶SmaI消化,用作PCR反应的模板,PCR反应用合成的DNA寡核苷酸126终止片段(SEQ ID NO:68)和125起始片段(SEQ ID NO:69)作引物,结果扩增出一条576碱基对的DNA片段。扩增片段用限制性内切酶HindIII和NcoI消化,结果产生一条558碱基对的HindIII、NcoI片段。质粒pMON 13181的DNA用HindIII和AflIII消化,结果产生一条4068碱基对的HindIII、AflIII片段。连接限制性片段,连接反应混合液用于转化大肠杆菌k-12 JM 101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,用限制性分析及测序证实正确插入。质粒pMON15966含有编码下列氨基酸序列的(SEQ ID NO:158)DNA序列:MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGly(SEQ ID NO:198)
实施例50
pMON 15967的构建
所构建的pMON 15967是一种含编码多功能性造血受体激动剂的DNA序列的质粒。质粒pMON 15960的DNA用限制性内切酶SmaI消化,用作PCR反应的模板,PCR反应的引物用合成的DNA寡核苷酸132终止引物(SEQ ID NO:71)和133起始引物(SEQ ID NO:70),结果扩增出一条576碱基对的DNA片段。扩增片段用限制性内切酶HindIII和NcoI消化,结果产生一条558碱基对的HindIII、NcoI片段。质粒pMON 13181的DNA用HindIII和AflIII消化,结果产生一条4068碱基对的HindIII、AflIII片段。连接限制性片段,连接反应混合液用于转化大肠杆菌k-12 JM101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,用限制性分析及测序证实正确插入。质粒pMON15967含有编码下列氨基酸序列的(DEQ ID NO:159)DNA序列:MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
实施例51
pMON 13180,一种用于构建含有编码多功能造血受体激动剂的 DNA序列的质粒的中介质粒的构建。
质粒pMON 13046(WO 95/21254)的DNA用限制性核酸内切酶XmaI和SnaBI消化,结果产生一条4018碱基对的载体片段。4018碱基对的XmaI-SnaBI片段用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化,其中25碱基对的XmaI-SnaBI插入片段没有保留。设计合成寡核苷酸的互补对glyxa1(SEQ ID NO:74)和glyxa2(SEQ ID NO:75)以移去编码Xa因子裂解位点的序列。当合适装配时,这些寡核苷酸也产生XmaI和SnaBI末端。经70℃加热10分钟,然后缓慢冷却,引物Glyxa1和Glyxa2在退火缓冲液(20mM Tris-HClpH7.5,10mM MgCl2,50mM NaCl)中退火。用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN),连接来自pMON 13046的4018碱基对的XmaI-SnaBI片段和装配的寡核苷酸部分连接反应液用于转化大肠杆菌DH5α菌株细胞(生命技术公司,Gaithersburg,MD)。在含有氨苄青霉素的平皿上挑选出转化的细菌从转化体中分离质粒DNA,用基于PCR的方法分析。来自选出的转化体的质粒DNA被测序以证实寡核苷酸的正确插入。产生的质粒称为pMON 3180,含有(SEQ ID NO:**)的DNA序列。
实施例52
pMON 3181,一种用于构建含有编码多功能性造血受体激动剂的
DNA序列的质粒的中介质粒的构建
质粒pMON 13047(WO 95/21254)的DNA用限制性核酸内切酶XmaI和SnaBI消化,结果产生一条4063碱基对的载体片段。4063碱基对的XmaI-SnaBI片段用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化,其中25碱基对的XmaI-SnaBI插入片段没有保留。设计合成的寡核苷酸互补对glyxa1(SEQ ID NO:74)和glyxa2(SEQ ID NO:75),以移去编码Xa因子裂解位点的序列。当适当装配时,这些寡核苷酸也产生XmaI和SnaBI末端。经70℃加热10分钟,然后缓慢冷却,Glyxa1和Glyxa2在退火缓冲液中退火。用T4 DNA连接酶,连接来自pMON 13047的4063碱基对的XmaI-SnaBI片段和装配的寡核苷酸。部分连接反应液用于转化大肠杆菌DH5α菌株细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。从转化体中分离质粒DNA,用基于PCR的方法分析。来自选出的转化体的质粒DNA被测序,以证实寡核苷酸的正确插入。产生的质粒称为pMON 13181,含有(SEQ ID NO:**)的DNA序列。
实施例53
pMON 13182的构建
用材料和方法中所述的方法I,产生在pMON 13182中的新N-末端/C-末端基因。用引物组39起始引物(SEQ ID NO:64)和L-11起始引物(SEQID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组38终止引物(SEQ ID NO:65)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用39起始引物和38终止引物,扩增退火的起始和终止片段而产生全长新N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13180被限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13182。
用pMON 13182转化大肠杆菌JM 101菌株,以表达蛋白和从包含体中分离蛋白。
质粒pMON 13182含有编码下列氨基酸序列的(SEQ ID NO:94)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AsP Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr(SEQ ID NO:166)
实施例54
pMON 13183的构建
用在材料和方法中所述的方法I,产生在pMON 13183中的新N-末端/C-末端的基因。用引物组39起始引物(SEQ ID NO:64)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生“起始片段”。用引物组38终止引物(SEQ ID NO:65)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用39起始引物和38终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSFSer17。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13181被限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化片段。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON13183。
为表达蛋白和从包含体中分离蛋白,用pMON 13183转化大肠杆菌JM 101菌株。
质粒pMON 13183含有编码下列氨基酸序列的(SEQ ID NO:95)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr(SEQ ID NO:167)
实施例55
pMON 13184的构建
用在材料和方法中所述的方法I,产生在pMON 13184中的新N-末端/C-末端基因。用引物组97起始引物(SEQ ID NO:66)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组96终止引物(SEQ ID NO:67)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用97起始引物和96终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean up试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13180被限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化片段。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13184。
为表达蛋白和从包含体中分离蛋白,用pMON 13184转化大肠杆菌JM 101菌株。
质粒pMON 13184含有编码下列氨基酸序列的(SEQ ID NO:96)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser(SEQ ID NO:168)
实施例56
pMON 13185的构建
用在材料和方法中所述的方法I,产生在pMON 13185中的新N-末端/C-末端基因。用引物组97起始引物(SEQ ID NO:66)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组96终止引物(SEQ ID NO:67)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用97起始引物和96终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化片段。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON13185。
为表达蛋白和从包含体中分离蛋白,用pMON 13185转化大肠杆菌JM 101菌株。
质粒pMON 13185含有编码下列氨基酸序列的(SEQ ID NO:67)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser(SEQ ID NO:169)
实施例57
pMON 13186的构建
用材料和方法中所述的方法I产生在pMON 13186中的新N-末端/C-末端基因。用引物组126起始引物(SEQ ID NO:68)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组125终止引物(SEQ ID NO:69)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用126起始引物和125终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化片段。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON13186。
为表达蛋白和从包含体中分离蛋白,用pMON 13186转化大肠杆菌JM 101菌株。
质粒pMON 13186含有编码下列氨基酸序列的(SEQ ID NO:98)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProSer Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln LeuHis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu GluGly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln LeuAsp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu GluLeu Gly(SEQ ID NO:170)
实施例58
pMON 13187的构建
用在材料和方法中所述的方法I,产生在pMON 13187中的新N-末端/C-末端基因。用引物组126起始引物(SEQ ID NO:68)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组125终止引物(SEQ ID NO:69)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用126起始引物和125终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13187。
为表达蛋白和从包含体中分离蛋白,用pMON 13187转化大肠杆菌JM 101菌株。
质粒pMON 13187含有编码下列氨基酸序列的(SEQ ID NO:99)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProSer Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln LeuHis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu GluGly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln LeuAsp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu GluLeu Gly(SEQ ID NO:171)
实施例59
pMON 13188的构建
用在材料和方法中所述的方法I,产生在pMON 13188中的新N-末端/C-末端基因。用引物组133起始引物(SEQ ID NO:70)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组132终止引物(SEQ ID NO:71)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用133起始引物和132终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。质粒pMON 13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13188。
为表达蛋白和从包含体中分离蛋白,用pMON 13188转化大肠杆菌JM 101菌株。
质粒pMON 13188含有编码下列氨基酸序列的(SEQ ID NO:100)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly SerGln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile GlnGly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu GlnLeu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu TyrGln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro(SEQ ID NO:172)
实施例60
pMON 13189的构建
用在材料和方法中所述的方法I,产生在pMON 13189中的新N-末端/C-末端基因。用引物组133起始引物(SEQ ID NO:70)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组132终止引物(SEQ ID NO:71)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列。用133起始引物和132终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13189。
为表达蛋白和从包含体中分离蛋白,用pMON 13189转化大肠杆菌JM 101菌株。
质粒pMON 13189含有编码下列氨基酸序列的(SEQ ID NO:101)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly SerGln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile GlnGly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu GlnLeu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu TyrGln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro(SEQ ID NO:173)
实施例61
pMON 13190的构建
用在材料和方法中所述的方法I,产生在pMON 13190中的新N-末端/C-末端基因。用引物组142起始引物(SEQ ID NO:72)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组141终止引物(SEQ ID NO:73)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列。用142起始引物和141终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13190。
为表达蛋白和从包含体中分离蛋白,用pMON 13190转化大肠杆菌JM 101菌株。
质粒pMON 13190含有编码下列氨基酸序列的(SEQ ID NO:102)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Sar Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu AspVal Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro AlaPhe Ala(SEQ ID NO:l74)
实施例62
pMON 13191的构建
用在材料和方法中所述的方法I,产生在pMON 13191中的新N-末端/C-末端基因。用引物组142起始引物(SEQ ID NO:72)和L-11起始引物(SEQ ID NO:60),扩增在pMON 13037中的G-CSF Ser17序列而产生起始片段。用引物组141终止引物(SEQ ID NO:73)和L-11终止引物(SEQ ID NO:61),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。用142起始引物和141终止引物扩增退火的起始和终止片段,而产生全长新的N-末端/C-末端G-CSF Ser17基因。
产生的含有新基因的DNA片段经限制性核酸内切酶NcoI和HindIII消化,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。中介质粒pMON 13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,IndianapoIis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 13191。
为表达蛋白和从包含体中分离蛋白,用pMON 13191转化大肠杆菌JM 101菌株。
质粒pMON 13191含有编码下列氨基酸序列的(SEQ ID NO:103)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu AspVal Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro AlaPhe Ala(SEQ ID NO:175)
实施例63
pMON 13192的构建
用在材料和方法中所述的方法II,产生在pMON 13192的新N-末端/C-末端的基因。用引物组39起始引物(SEQ ID NO:64)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSF序列而产生起始片段。用引物组38终止引物(SEQ ID NO:65)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSFSer17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含有全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON 13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正常插入。产生的质粒称为pMON 13192。
为表达蛋白和从内含体中分离蛋白,用pMON 13192转化大肠杆菌JM 101菌株。
质粒pMON 13192含有编码下列氨基酸序列的(SEQ ID NO:104)DNA序列:13192.PeptAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr(SEQ ID NO:176)
实施例64
pMON 13192的构建
用在材料和方法中所述的方法II,产生在pMON 13193中的新N-末端/C-末端的基因。用引物组39起始引物(SEQ ID NO:64)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组38终止引物(SEQ ID NO:65)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化,纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含有全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista、CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON 13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 13193。
为表达蛋白和从包含体中分离蛋白,用pMON 13193转化大肠杆菌JM 101菌株。
质粒pMON 13193含有编码下列氨基酸序列的(SEQ ID NO:105)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys argPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr(SEQ ID NO:177)
实施例65
pMON 25190的构建
用在材料和方法中所述的方法II,产生在pMON 25190中的新N-末端/C-末端基因。用引物组97起始引物(SEQ ID NO:66)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSF序列而产生起始片段。用引物组96终止引物(SEQ ID NO:67)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正常插入。产生的质粒称为pMON 25190。
为表达蛋白和从包含体中分离蛋白,用pMON 25190转化大肠杆菌JM 101菌株。
质粒pMON 25190含有编码如下氨基酸序列的(SEQ ID NO:106)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser(SEQ ID NO:178)
实施例66
pMON 25191的构建
用在材料和方法中所述的方法II,产生在pMON 25191中的新N-末端/C-末端基因。用引物组97起始引物(SEQ ID NO:66)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 1 3037中的G-CSF Ser17序列而产生起始片段。用引物组96终止引物(SEQ ID NO:98)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSFSer17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,被连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 25191。
为表达蛋白和从包含体中分离蛋白,用pMON 25191转化大肠杆菌JM 101菌株。
质粒pMON 25191含编码下列氨基酸序列的(SEQ ID NO:107)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser(SEQ ID NO:179)
实施例67
pMON13194的构建
用在材料和方法中所述的方法II,产生在pMON13194中的新N-末端/C-末端基因。用引物组126起始引物(SEQ ID NO:68)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组125终止引物(SEQ ID NO:67)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON13180被限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 13194。
为表达蛋白和从包含体中分离蛋白,用pMON 13194转化大肠杆菌JM 101菌株。
质粒pMON 13194含有编码下列氨基酸序列的(SEQ ID NO:108)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProThr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu LeuLys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala AlaLeu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro GluGlu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala ProLeu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys LeuSer Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln GlnMet Glu Glu Leu Gly(SEQ ID NO:180)
实施例68
pMON 13195的构建
用在材料和方法中所述的方法II,产生在pMON 13195中的新N-末端/C-末端基因。用引物组126起始引物(SEQ ID NO:68)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组125终止引物(SEQ ID NO:69)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含有全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON 13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boe hringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 13195。
为表达蛋白和从包含体中分离蛋白,用pMON 13195转化大肠杆菌JM 101菌株。
质粒pMON 13195含有编码下列氨基酸序列的(SEQ ID NO:109)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProThr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu LeuLys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala AlaLeu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro GluGlu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala ProLeu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys LeuSer Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln GlnMet Glu Glu Leu Gly(SEQ ID NO:181)
实施例69
pMON 13196的构建
用在材料和方法中所述的方法II,产生在pMON 13196中的新N-末端/C-末端基因。用引物组133起始引物(SEQ ID NO:70)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSF序列而产生起始片段。用引物组132终止引物(SEQ ID NO:71)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSFSer17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含有全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON 13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 13196。
为表达蛋白和从包含体中纯化蛋白,用pMON 13196转化大肠杆菌JM 101菌株。
质粒pMON 13196含有编码下列氨基酸序列的(SEQ ID NO:110)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val ArgLys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys AlaThr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly HisSer Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser GlnAla Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser ProGlu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala AspPhe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met AlaPro Ala Leu Gln Pro(SEQ ID NO:182)
实施例70 pMON 13197的构建
用在材料和方法中所述的方法II,产生在pMON 13197中的新N-末端/C-末端基因。用引物组133起始引物(SEQ ID NO:70)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组132终止引物(SEQ ID NO:71)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含有全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON13181经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 13197。
为表达蛋白和从包含体中分离蛋白,用pMON 13197转化大肠杆菌JM 101菌株。
质粒pMON 13197含有编码下列氨基酸序列的(SEQ ID NO:111)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSar Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr(SEQ ID NO:183)
实施例71
pMON 13198的构建
用在材料和方法中所述的方法II,产生在pMON 13198中的新N-末端/C-末端基因。用引物组142起始引物(SEQ ID NO:72)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSF序列而产生起始片段。用引物组141终止引物(SEQ ID NO:73)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSFSer17序列而产生终止片段。起始片段被限制性核酸内切酶NcoI消化,而终止片段被限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON13180经限制性核酸内切酶HindIII和AflIII消化,结果产生一条4023碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON13198。
为表达蛋白和从包含体中分离蛋白,用pMON 13198转化大肠杆菌JM 101菌株。
质粒pMON 13198含有编码下列氨基酸序列的(SEQ ID NO:112)DNA序列:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu
Leu Val Leu Leu Gly His Sar Leu Gly Ile Pro Trp Ala Pro Leu
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Mat
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala
Met Pro Ala Phe Ala(SEQ ID NO:184)
实施例72
pMON 13199的构建
用在材料和方法中所述的方法II,产生在pMON 13199中的新N-末端/C-末端基因。用引物组142起始引物(SEQ ID NO:72)和P-bl起始引物(SEQ ID NO:62),扩增在pMON 13037中的G-CSFSer17序列而产生起始片段。用引物组141终止引物(SEQ ID NO:73)和P-bl终止引物(SEQ ID NO:63),扩增在pMON 13037中的G-CSF Ser17序列而产生终止片段。起始片段用限制性核酸内切酶NcoI消化,而终止片段用限制性核酸内切酶HindIII消化。纯化后,消化过的起始和终止片段合并在一起,连接到pMON 3934的约3800碱基对的NcoI-HindIII载体片段上。
上述的中介质粒含全长新的N-末端/C-末端G-CSF Ser17基因,用限制性核酸内切酶NcoI和HindIII消化,消化过的DNA在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离全长新的N-末端/C-末端G-CSF Ser17基因。中介质粒pMON13181用限制性核酸内切酶HindIII和AflIII消化,结果产生一条4068碱基对的载体片段,用Magic DNA Clean-up方法试剂盒(Promega,Madison,WI)纯化。合并纯化的限制性片段,用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN)连接。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实新基因的正确插入。产生的质粒称为pMON 13199。
为表达蛋白和从包含体中分离蛋白,用pMON 13199转化大肠杆菌JM 101菌株。
质粒pMON 13199含有编码下列氨基酸序列的(SEQID NO:113)DNA序列:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr LeuGln Leu Asr Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln MetGlu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly AlaMet Pro Ala Phe Ala (SEQ ID NO:185)
实施例73
构建串联重复质粒模板,Syntanl
为产生串联重复的hIL-3受体激动剂pMON 13416模板,Syntanl,用T4DNA连接酶(Boehringer Mannheim)连接的方法,连接三种DNAs。这三种DNAs是:1)pMON 13046,含有hIL-3受体激动剂pMON 13416,用BstEII和SnaBI消化;2)合成寡核苷酸的退火互补对,Llsyn.for(SEQ ID NO:48)和Llsyn.rev(SEQ IDNO:49),该互补对含有编码连接原始蛋白的C-末端和N-末端和pMON 13416周围序列的小部分的接头的序列,当合适装配时会产生BstEII和CbaI端;3)用ClaI(DNA在dam-细胞中生长,DM1(生命技术公司))和SnaBI从pMON 13046消化而来的hIL-3受体激动剂pMON 13416部分。消化过的DNAs在0.9%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101)分离。
部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。从转化体中分离制取微量DNA,用基于PCR的方法筛选转化体。来自选出的转化体中的质粒DNA被测序以得到正确的模板。产生的质粒称为Syntanl,含有(SEQ ID NO:84)的DNA序列。
实施例74
构建串联重复模板,Syntan3
为产生串联重复的hIL-3受体激动剂pMON 13416模板Syntan3,用T4 DNA连接酶(Boehringer Mannheim)连接的方法连接三种DNAs。这三种DNA是:1)pMON 13046,含有hIL-3受体激动剂pMON 13416;用BstEII和SnaBI消化;2)合成寡核苷酸的退火互补对,L3syn.for(SEQ ID NO:50)和L3syn.rev(SEQ ID NO:51),这些互补对含有编码接头的序列,该接头连接原始蛋白的C-末端和N-末端及pMON 13416周围序列的小部分。当互补对适当装配时产生BstEII和SnaBI端;3)用ClaI(DNA在dam-细胞中生长,DM1(生命技术公司))和SnaBI从pMON 13046消化而来的hIL-3受体激动剂pMON 13416部分。消化过的DNA在0.9%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101)分离。
部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。从转化体中分离制取微量DNA,用基于PCR的方法筛选转化体。从选出的转化体中来的质粒DNA被测序,以获得正确模板。产生的质粒称为Syntan3,含有(SEQ ID NO:85)的DNA序列。
实施例75
pMON 31104的构建
用在材料和方法中所述的方法III,产生在pMON 31104中的新N-末端/C-末端基因。用引物组35起始引物(SEQID NO:52)和34反向引物(SEQ ID NO:53)从中介质粒Syntanl扩增,而产生hIL-3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31104。
为表达蛋白和从包含体中分离蛋白,用pMON 31104转化大肠杆菌JM 101菌株。
质粒pMON 31104含有编码下列氨基酸序列的(SEQ ID NO:86)DNA序列:Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg AlaVal Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu ArgAsn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser ArgHis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg GluLys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile IleHis His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQID NO:186)
实施例76
pMON 31105的构建
用在材料和方法中所述的方法III,产生在pMON 31105中的新N-末端/C-末端基因。用引物组70起始引物(SEQ ID NO:54)和69反向引物(SEQ ID NO:55)从中介质粒Syntanl上扩增,而产生hIL3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31105。
为表达蛋白和从包含体中分离蛋白,用pMON 31105转化大肠杆菌JM 101菌株。
质粒pMON 31105含有编码下列氨基酸序列的(SEQ ID NO:87)DNA序列:Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile IleLys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe TyrLeu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly SerAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro (SEQID NO:187)
实施例77
pMON 31106的构建
用在材料和方法中所述的方法III,产生在pMON 31106中的新N-末端/C-末端基因。用引物组91起始引物(SEQ ID NO:56)和90反向引物(SEQ ID NO:57)从中介质粒Syntanl中扩增,而产生hIL3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化。消化过的DNA片段在1%TAE凝胶分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4DNA连接酶(BoehringerMannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,以移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31106。
为表达蛋白和从包含体中分离蛋白,用pMON 31106转化大肠杆菌JM 101菌株。
质粒pMON 31106含有编码下列氨基酸序列的(SEQ ID NO:80)DNA序列:Ala Pro Sel Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu LeuAsp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met AspArg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala ValLys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg AsnLeu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro (SEQID NO:188)
实施例78
pMON 31107的构建
用在材料和方法中所述的方法III,产生在pMON 31107中的新N-末端/C-末端基因。用引物组101起始引物(SEQ ID NO:58)和100反向引物(SEQ ID NO:59)从中介质粒Syntanl中扩增,而产生hIL-3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4 DNA连接酶(Boehringer Mannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,以移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经在0.8%TAE凝胶上分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31107。
为表达蛋白和从包含体中纯化蛋白,用pMON 31107转化大肠杆菌JM 101菌株。
质粒pMON 31107含有编码下列氨基酸序列的(SEQ ID NO:89)DNA序列:Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr LeuVal Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser AsnCys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg ProPro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp ValSer Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu SerPhe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile GluAla Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Tyr Val Glu Gly GlyGly Gly Ser Prc Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Sar Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro (SEQ ID NO:189)
实施例79
pMON 31108的构建
用在材料和方法中所述的方法III,产生在pMON 31108中的新N-末端/C-末端基因。用引物组35起始引物(SEQ ID NO:52)和34反向引物(SEQ ID NO:53)从中介质粒Syntan3中扩增,而产生hIL-3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,经溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4 DNA连接酶(BoehringerMannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,以移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31108。
为表达蛋白和从包含体中分离蛋白,用pMON 31108转化大肠杆菌JM 101菌株。
质粒pMON 31108含有编码下列氨基酸序列的(SEQ ID NO:90)DNA序列:Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg AlaVal Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu ArgAsn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser ArgHis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg GluLys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn CysSer Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro ProAla Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Prc TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro (SEQID NO:190)
实施例80
pMON 31109的构建
用在材料和方法中所述的方法III,产生在pMON 31109中的新N-末端/C-末端基因。用引物组70起始引物(SEQ ID NO:54)和69反向引物(SEQ ID NO:55)从中介质粒Syntan3中扩增,而产生hIL-3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4DNA连接酶(BoehringerMannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,以移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31109。
为表达蛋白和从包含体中分离蛋白,用pMON 31109转化大肠杆菌JM 101菌株。
质粒pMON 31109含有编码下列氨基酸序列的(SEQ ID NO:9 1)DNA序列:Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile IleLys Ala Gly Asp Trp GLn Glu Phe Arg Glu Lys Leu Thr Phe TyrLeu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly SerGly Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu AspPro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp ArgAsn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val LysAsn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro (SEQID NO:191)
实施例81
pMON 31110的构建
用在材料和方法中所述的方法III,产生在pMON 31110中的新N-末端/C-末端基因。用引物组91起始引物(SEQ ID NO:56)和96反向引物(SEQ ID NO:57)从中介质粒Syntan3中扩增,而产生hIL-3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,用溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4 DNA连接酶(BoehringerMannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,以移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31110。
为表达蛋白和从包含体中分离蛋白,用pMON 31110转化大肠杆菌JM 101菌株。
质粒pMON 31110含有编码下列氨基酸序列的(SEQ ID NO:92)DNA序列:Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly GlyGly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro (SEQID NO:192)
实施例82
pMON 31111的构建
用在材料和方法中所述的方法III,产生在pMON 31111中的新N-末端/C-末端基因。用引物组101起始引物(SEQ ID NO:58)和100反向引物(SEQ ID NO:59)从中介质粒Syntan3中扩增,而产生hIL-3受体激动剂pMON 13416的全长新的N-末端/C-末端基因。
产生的含有新基因的DNA片段,用限制性核酸内切酶NcoI和SnaBI消化,消化过的DNA片段在1%TAE凝胶上分离,经溴化乙锭染色,用Geneclean(Bio101,Vista,CA)分离。用T4 DNA连接酶(BoehringerMannheim,Indianapolis,IN),把纯化的消化DNA片段连接到表达载体pMON 13189上。pMON 13189 DNA预先已用NcoI和SnaBI消化,以移去hIL3受体激动剂pMON 13416编码序列,4254碱基对的载体片段经0.8%TAE凝胶分离和溴化乙锭染色后,用Geneclean(Bio101,Vista,CA)分离。部分连接反应液用于转化大肠杆菌菌株DH5α细胞(生命技术公司,Gaithersburg,MD)。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,测序以证实正确插入。产生的质粒称为pMON 31111。
为表达蛋白和从包含体中分离蛋白,用pMON 31111转化大肠杆菌JM 101菌株。
质粒pMON 31111含有编码下列氨基酸序列的(SEQ ID NO:93)DNA序列: Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr LeuVal Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser GlyGly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp GluIle Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp ProAsn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg AsnLeu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys AsnLeu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro (SEQID NO:193)
实施例83
pMON 31112的构建
所构建的pMON 31112是一种含有编码多功能性造血受体激动剂的DNA序列的质粒,该激动剂活化hIL-3受体和G-CSF受体。质粒pMON 13189 DNA用限制性内切酶NcoI和XmaI消化,从0.8%琼脂糖凝胶中分离和纯化,结果产生一条NcoI,XmaI载体片段。来自第二种质粒pMON 13222(WO 94/12639,美国专利系列号# 08/411,796)的DNA,用NcoI和EcoRI消化,结果产生一条281碱基对的NcoI,EcoRI片段。该片段从1.0%琼脂糖凝胶中分离和纯化。二种寡核苷酸SYNNOXA1.REQ(SEQ ID NO:240)和SYNNOXA2.REQ(SEQ IDNO:241)退火,和来自pMON 13222的281碱基对的DNA片段一起连接到来自pMON 13189的DNA载体片段上。然后,部分连接反应混合液转化到k-12大肠杆菌JM 101菌株中。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,由限制性分析显示存在EcoRV片段,测序以证实正确插入。
质粒pMON 31112含有编码下列氨基酸序列的(SEQ ID NO:114)DNA序列:MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLauSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLauLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQID NO:199)
实施例84
pMON 31113的构建
所构建的pMON 31113是一种含有编码多功能性造血受体激动剂的DNA序列的质粒,该激动剂活化hIL-3受体和G-CSF受体。质粒pMON 13197的DNA用限制性内切酶NcoI和XmaI消化,从0.8%琼脂糖凝胶中分离和纯化,结果产生一条NcoI,XmaI载体片段。来自第二种质粒pMON 13239(WO94/12639,美国专利系列号# 08/411,796)的DNA,用NcoI和EcoRI消化,结果产生一条281碱基对的NcoI,EcoRI片段。该片段从1.0%琼脂糖凝胶中分离和纯化。二种寡核苷酸SYNNOXA1.REQ(SEQ ID NO:240)和SYNNOXA2.REQ(SEQ IDNO:241)退火,和来自pMON 13239的281碱基对的DNA片段一起连接到来自pMON 13197的DNA载体片段上。然后,部分连接反应混合液转化到k-12大肠杆菌JM 101菌株中。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,由限制性分析显示存在EcoRV片段,测序以证实正确插入。
质粒pMON 31113含有编码下列氨基酸序列的(SEQ ID NO:115)DNA序列:MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAsoValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro (SEQID NO:200)
实施例85
pMON 31114的构建
所构建的pMON 31114是一种含有编码多功能性造血受体激动剂的DNA序列的质粒,该激动剂活化hIL-3受体和G-CSF受体。质粒pMON 13189的DNA用限制性内切酶NcoI和XmaI消化,从0.8%琼脂糖凝胶中分离和纯化,结果产生一条NcoI,XmaI载体片段。来自第二种质粒pMON 13239(WO94/12639,美国专利系列号# 08/411,796)的DNA,用NcoI和EcoRI消化,结果产生一条28I碱基对的NcoI,EcoRI片段。该片段从1.0%琼脂糖凝胶中分离和纯化。二种寡核苷酸SYNNOXA1.REQ(SEQ ID NO:240)和SYNNOXA2.REQ(SEQ IDNO:241)退火,和来自pMON 13239的281碱基对的DNA片段一起连接到来自pMON 13189的DNA载体片段上。然后,部分连接反应混合液转化到k-12大肠杆菌JM 101菌株中。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,由限制性分析显示存在EcoRV片段,测序以证实正确插入。
质粒pMON 31114含有编码下列氨基酸序列的(SEQ ID NO:116)DNA序列:MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLauValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:201)
实施例86
pMON 31115的构建
所构建的pMON 31115是一种含有编码多功能性造血受体激动剂的DNA序列的质粒,该激动剂活化hIL-3受体和G-CSF受体。质粒pMON 13197的DNA用限制性内切酶NcoI和XmaI消化,从0.8%琼脂糖凝胶中分离和纯化,结果产生一条NcoI,XmaI载体片段。来自第二种质粒pMON 13222的DNA用NcoI和EcoRI消化,结果产生一条281碱基对的NcoI,EcoRI片段。该片段从1.0%琼脂糖凝胶中分离和纯化。二种寡核苷酸SYNNOXA1.REQ(SEQ ID NO:240)和SYNNOXA2.REQ(SEQ ID NO:241)退火,和来自pMON 13222的281碱基对的DNA片段一起连接到来自pMON 13197的DNA载体片段上。然后,部分连接反应混合液转化k-12大肠杆菌JM 101菌株。在含氨苄青霉素的平皿上挑选出转化的细菌。分离质粒DNA,由限制性分析显示存在EcoRV片段,测序以证实正确插入。
质粒pMON 31115含有编码下列氨基酸序列的(SEQ ID NO:117)DNA序列:MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEO ID NO:202)
实施例87
体外测定多功能性造血受体激动剂蛋白的活性
用基于亲和纯化的多克隆抗体的三明治ELISA法,能测定多功能性造血受体激动剂蛋白的蛋白浓度。替代的方法是蛋白浓度也能通过氨基酸组成分析测定。多功能性造血受体激动剂的生物活性能用许多体外测定法确定。例如,结合hIL-3受体和G-CSF受体的多功能性造血受体激动剂能用表达hIL-3和/或G-CSF受体的细胞系及细胞增殖测定法加以鉴定。一种上述的测定法是AML-193细胞增殖测定法。AML-193细胞对IL-3和G-CSF应答而顾及被测的IL-3/G-CSF多功能性造血受体激动剂的结合生物活性。另一种上述测定法是TF1细胞增殖测定法。
此外,可用其他依赖因子的细胞系,如依赖于鼠IL-3的细胞系M-NFS-60(ATCC,CRL 1838)或32D。IL-3的活性有物种特异性而G-CSF没有,因此,IL-3/G-CSF多功能性造血受体激动剂的G-CSF组分的生物活性能分别地测定。不表达针对特定配体的受体的细胞系如BHK或鼠Baf/3,能用含有编码所需受体的基因的质粒转染。上述细胞系的一个实施例是用hG-CSF受体转染过的BaF3(BaF3/hG-CSF)。在这些细胞系中,多功能性造血受体激动剂的活性能与hIL-3或G-CSF单独或一起使用做比较。用BaF3/hG-CSF细胞增殖测定法和TF1细胞增殖测定法测定本发明的多功能造血细胞受体激动剂的实施例,在表5和表6显示。多功能性造血细胞受体激动剂的生物活性,以与标准蛋白pMON 13056(WO 95/21254)相比的相对活性表示。用BaF3/c-mpl细胞增殖测定法和TF1细胞增殖测定法测定本发明的多功能性造血受体激动剂生物活性的实施例,在表7和表8显示。
表5
双重IL-3/G-CSF受体激动剂的细胞增殖活性
pMoN | BaF3/hG-CSF受体细胞增殖测定法相对活性* | TFI细胞增殖测定法相对活性* |
13182 | 0.015 | 1.1 |
13183 | 0.02 | nd |
13184 | 0.01 | 0.3 |
13185 | 0.023 | 0.36 |
13186 | 0.36 | 0.45 |
13187 | 0.07 | 0.26 |
13188 | 0.64 | 1.3 |
13189 | 0.58 | 1.37 |
13190 | 0.045 | 1.2 |
13191 | 0.14 | 2.7 |
13192 | 0.09 | 2.2 |
13193 | 0.06 | 3.0 |
25190 | nd | nd |
25191 | 0.43 | 1.2 |
13194 | nd | nd |
13195 | 1.3 | 4.3 |
13196 | 0.66 | 0.5 |
13197 | 0.6 | 0.77 |
13198 | 0.6 | 0.5 |
13199 | nd | nd |
15982 | 0.7 | 1.9 |
15981 | 0.068 | 1.2 |
15965 | 0.7 | 0.82 |
15966 | 0.36 | 1.48 |
15967 | 0.62 | 1.37 |
nd=未测定
*多功能性造血受体激动剂的生物活性,以与标准蛋白pMON 13056比较的相对活性表示。n=3或更多
表6
双重IL-3/G-CSF受体激动剂的细胞增殖活性
pMoN | BaF3/hG-CSF受体细胞增殖测定法相对活性 | TFI细胞增殖测定法相对活性 |
31104 | + | + |
31105 | + | + |
31106 | + | + |
31107 | nd | nd |
31108 | + | + |
31109 | + | + |
31110 | nd | nd |
31111 | nd | nd |
31112 | + | + |
31113 | + | + |
31114 | + | + |
31115 | + | + |
31116 | nd | nd |
31117 | nd | nd |
nd=未测定
+多功能性造血受体激动剂的生物活性(n=1或2),以与标准蛋白pMON 13056比较的相对活性表示。
“+”显示该分子与pMON 13056相类似。
表7
细胞增殖活性
pMON | Baf3/c-mpl受体细胞增殖测定活性* | TFI细胞增殖测定活性 |
28505 | - | + |
28506 | - | + |
28507 | - | + |
28508 | - | + |
28509 | - | + |
28510 | - | + |
28511 | + | + |
28512 | + | + |
28513 | + | + |
28514 | + | + |
28519 | - | + |
28520 | - | + |
28521 | - | + |
28522 | - | + |
28523 | - | + |
28524 | - | + |
28525 | + | + |
28526 | + | + |
28533 | - | + |
28534 | - | + |
28535 | - | + |
28536 | - | + |
28537 | - | + |
28538 | - | + |
28539 | + | + |
28540 | + | + |
28541 | + | + |
28542 | + | + |
28543 | + | + |
28544 | + | + |
28545 | + | + |
*相对于c-mpl配体(1-153),在Baf3细胞系用c-mpl受体转染测定的活性
+相对于pMON 13056测定的活性
用相似的方法,本领域的技术人员熟知的其他依赖因子的细胞系能用于测定需测的多功能性造血受体激动剂的生物活性。能用甲基纤维素测定法测定多功能性造血受体激动剂体外对造血祖细胞和不同类型的造血细胞集落的模式的影响。甲基纤维素测定法能提供前体细胞发生率的估计值,因为该法测定每100,000个输入细胞的祖细胞发生率。长期、基质依赖的培养法已用于描斜原始造血祖细胞和干细胞。该测定法能用于测定多功能性造血受体激动剂是否刺激非常原始祖细胞和/或干细胞的扩增。此外,能进行有限稀释培养法,该法由多功能性造血受体激动剂刺激的原始祖细胞发生率。
表8
pMON# | IL-3激动剂活性(AML细胞增殖测定法) | c-mpl受体激动剂活性(Baf/3-c-mpl细胞增殖测定法) |
28505 | + | - |
28506 | + | - |
28507 | + | - |
28508 | + | - |
28509 | + | - |
28510 | + | - |
28511 | + | + |
28512 | + | + |
28513 | + | + |
28514 | + | + |
28515 | + | + |
28519 | + | - |
28520 | + | - |
28521 | + | - |
28522 | + | - |
28523 | + | - |
28524 | + | - |
28525 | + | - |
28526 | + | + |
28527 | + | + |
28528 | + | + |
28529 | + | + |
表8(续)
实施例88
28535 | + | - |
28539 | + | + |
28540 | + | + |
28541 | + | + |
28542 | + | + |
28545 | + | + |
28551 | + | + |
28571 | + | + |
用在WO 94/12369和WO 94/12638所述的PCR诱变技术,制取含单一或多种氨基酸替换的G-CSF变异体。用种种其他方法包括合成基因装配或定点诱发(见Taylor等,核苷酸研究13:7864-8785[1985];Kunkel等,美国国家科学院院报82:488-492[1985];Sambrook等,分子克隆:实验室手册,第2版,冷泉港实验室出版社,冷泉港,NY[1989],(WO94/12639)和(WO94/12638)),本领域的技术人员也能制取这些和其他变异体(即氨基酸替换,插入或缺失,以及N-末端或C-末端延伸)。这些替换一次做一个,或和其他氨基酸替换和/或缺失、和/或插入、和/或延伸联合进行。证实序列的变化后,为产生变异体,质粒DNA可转染到合适的哺乳动物细胞、昆虫细胞或诸如大肠杆菌的细菌菌株中。有活性的已知的G-CSF变异体包括在1位(Thr变为Ser、Arg或Gly)、2位(Pro变为Leu)、3位(Leu变为Arg或Ser)和17位(Cys变为Ser)的替换,以及氨基酸1-11的缺失(Kuga等,生物化学和生物物理研究通讯159:103-111(1989))。这些G-CSF氨基酸变异体能用作模板以产生G-CSF受体激动剂,其中产生了新N-末端和新C-末端。G-CSF氨基酸替换变异体的实施例在表9显示。
实施例89
G-CSF氨基酸替换变异体的生物活性测定
利用人G-CSF受体转染的Baf/3细胞系,G-CSF氨基酸替换变异体能被进行细胞增殖活性测定。相对于原始人G-CSF,G-CSF氨基酸替换变异体的生物活性的实施例在表9显示。“+”表示与原始G-CSF相似的活性,而“-”表示明显降低或没有测定到活性。
表9
在用人G-CSF受体转染的BAF3细胞系中,
G-CSF变异体的细胞增殖活性
氨基酸位置 原始氨基酸 突变氨基酸 活性- |
13 Phe Ser +13 Phe His +13 Phe Thr +13 Phe Pro +16 Lys Pro +16 Lys Ser +16 Lys Thr +16 Lys His +18 Leu Pro +18 Leu Thr +18 Leu His +18 Leu Cys +18 Leu Ile +19 Glu Ala -19 Glu Thr -19 Glu Arg -19 Glu Pro -19 Glu Leu -19 Glu Ser -22 Arg Tyr +22 Arg Ser +22 Aro Ala +22 Arg Thr +24 Ile Pro +24 Ile Leu +24 Ile Tyr + |
表9续
氨基酸位置 原始氨基酸 突变氨基酸 活性 |
27 Asp Gly +30 Ala Ile +30 Ala Leu +34 Lys Ser +43 His Gly +43 His Thr +43 His Val +43 His Lys +43 His Trp +43 His Ala +43 His Arg +43 His Cys +43 His Leu +44 Pro Arg +44 Pro Asp +44 Pro Val +44 Pro Ala +44 Pro His +44 Pro Gln +44 Pro Trp +44 Pro Gly +44 Pro Thr +45 Glu Ala +46 Glu Arg +47 Leu Thr +49 Leu Phe +49 Leu Arg +49 Leu Ser +50 Leu His +54 Leu His + |
表8续
氨基酸位置 原始氨基酸 突变氨基酸 活性 |
67 Gln Lys +67 Gln Leu +67 Gln Cys +70 Gln Pro +70 Gln Leu +70 Gln Arg +70 Gln Ser +104 Asp Gly +104 Asp Val +108 Leu Ala +108 Leu Val +108 Leu Arg +108 Leu Gly +108 Leu Trp +108 Leu Gln +115 Thr His +115 Thr Leu +115 Thr Ala +144 Phe His +144 Phe Arg +144 Phe Pro +144 Phe Leu +144 Phe Glu +146 Arg Gln +147 Arg Gln +156 His Asp -156 His Ser +156 His Gly + |
表8续
氨基酸位置 原始氨基酸 突变氨基酸 活性 |
159 Ser Arg +159 Ser Thr +159 Ser Tyr +159 Ser Val +159 Ser Gly +162 Glu Gly -162 Glu Trp +162 Glu Leu +163 Val Arg +163 Val Ala +163 Val Gly +165 Tyr Cys nd169 Ser Leu +169 Ser Cys -169 Ser Arg +170 His Arg +170 His Ser - |
*相对于原始hG-CSF的活性
nd=未测定
不用进一步详述,可以认为本领域的技术人员能用先前的描述,最大程度地利用本发明。因此,下列优选的具体实施例仅看作是说明性的,而不是以任何方式限制本公开内容的未涉及部分。
有关分子生物学技术、蛋白纯化和生物测定方法的更多细节可在WO94/12639,WO 94/12638,WO 95/20976,WO 95/21197,WO95/20977,WO 95/21254中找到,作为一个整体在此引入仅作参考。
如果在此已写出,在此引用的所有参考文献、专利或申请,作为一个整体引入仅作参考。
对本领域的技术人员来说,阅读本公开内容后并不违反本发明的精神和范围,将会明了各种其他实施例。可以预期所有上述其他实施例将包括在所附的权利要求范围之内。
序列表(1)一般信息:(i)申请人:
(A)姓名:G.D.Searle&Co.
(B)街道:P.O.Box 5110
(C)城市:芝加哥
(D)州名:伊利诺斯
(E)国家:美国
(F)邮政编码(ZIP):60680
(G)电话:(708)470-6501
(H)电传:(708)470-6881
(A)姓名:Monsanto公司
(B)街道:800 North Lindbergh Boulevard
(C)城市:圣·路易斯
(D)州名:密苏里
(E)国家:美国
(F)邮政编码(ZIP):63167
(G)电话:(314)647-3131
(H)电传:(314)694-5435(ii)发明题目:多功能性造血受体激动剂(iii)序列数目:258(iv)计算机可读形式:
(A)介质类型:软盘
(B)计算机:IBM PC兼容
(C)操作系统:PC-DOS/MS-DOS
(D)软件:PatentIn Release#1.0,Version#1.30(EPO)(v)当前申请资料:
申请号:US 2910(vi)在先申请资料:
(A)申请号:US 60/004,834
(B)申请日期:1995年10月5日(2)SEQ ID NO:1的信息:(i)序列特性:
(A)长度:174氨基酸
(B)类型:氨基酸
(C)链型:末知
(D)拓扑结构:末知(ii)分子类型:蛋白(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:1
(D)其他信息:/注释=“在第1位的Xaa是Thr、Ser、Arg、
Tyr或Gly;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:2
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(A)名称/关键词:修饰位点
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(A)名称/关键词:修饰位点
(B)位置:170
(D)其他信息:/注释=“在第170位的Xaa是His、Arg或
Ser;”(xi)序列描述:SEQ ID NO:1:
Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa Leu Leu Xaa
1 5 10 15
Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly Ala Xaa Leu Gln
20 25 30
Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa Xaa Glu Xaa Xaa Val
35 40 45
Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp Ala Pro Leu Ser Ser Xaa
50 55 60
Pro Ser Xaa Ala Leu Xaa Leu Ala Gly Xaa Leu Ser Gln Leu His Ser
65 70 75 80
Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
85 90 95
Pro Glu Leu Gly Pro Thr Leu Xaa Thr Leu Gln Xaa Asp Val Ala Asp
100 105 110
Phe Ala Xaa Thr Ile Trp Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro
115 120 125
Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa
130 135 140
Gln Xaa Xaa Ala Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe
145 150 155 160
Leu Xaa Xaa Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
165 170(2)SEQ ID NO:2的信息:(i)序列特性:
(A)长度:133个氨基酸
(B)类型:氨基酸
(C)链型:单链
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(D)其他信息:/注释=“在第18位的Xaa是Asn、His、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第22位的Xaa是Glu、Trp、
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(D)其他信息:/注释=“在第25位的Xaa是Thr、His、
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(A)名称/关键词:修饰位点
(B)位置:26
(D)其他信息:/注释=“在第26位的Xaa是His、Thr、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第27位的Xaa是Leu、Gly、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第28位的Xaa是Lys、Arg、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第29位的Xaa是Gln、Asn、
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(D)其他信息:/注释=“在第30位的Xaa是Pro、His、
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(D)其他信息:/注释=“在第31位的Xaa是Pro、Asp、
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(A)名称/关键词:修饰位点
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(A)名称/关键词:修饰位点
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(A)名称/关键词:修饰位点
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第46位的Xaa是Asp、Phe、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第47位的Xaa是Ile、Gly、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第48位的Xaa是Leu、Ser、
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(A)名称/关键词:修饰位点
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第50位的Xaa是Glu、Leu、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第52位的Xaa是Asn、His、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第53位的Xaa是Leu、Thr、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第54位的Xaa是Arg、Asp、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第55位的Xaa是Arg、Thr、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第56位的Xaa是Pro、Gly、
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(A)名称/关键词:修饰位点
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第58位的Xaa是Leu、Ser、
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(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第59位的Xaa是Glu、Tyr、
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(A)名称/关键词:修饰位点
(B)位置:60
(D)其他信息:/注释=“在第60位的Xaa是Ala、Ser、
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(A)名称/关键词:修饰位点
(B)位置:61
(D)其他信息:/注释=“在第61位的Xaa是Phe、Asn、
Glu、Pro、Lys、Arg或Ser;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:62
(D)其他信息:/注释=“在第62位的Xaa是Asn、His、
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(A)名称/关键词:修饰位点
(B)位置:63
(D)其他信息:/注释=“在第63位的Xaa是Arg、Tyr、
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(A)名称/关键词:修饰位点
(B)位置:64
(D)其他信息:/注释=“在第64位的Xaa是Ala、Asn、
Pro、Ser或Lys;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:65
(D)其他信息:/注释=“在第65位的Xaa是Val、Thr、
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(A)名称/关键词:修饰位点
(B)位置:66
(D)其他信息:/注释=“在第66位的Xaa是Lys、Ile、
Arg、Val、Asn、Glu或Ser;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:67
(D)其他信息:/注释=“在第67位的Xaa是Ser、Ala、
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(A)名称/关键词:修饰位点
(B)位置:68
(D)其他信息:/注释=“在第68位的Xaa是Leu、Val、
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(A)名称/关键词:修饰位点
(B)位置:69
(D)其他信息:/注释=“在第69位的Xaa是Gln、Ala、
Pro、Thr、Glu、Arg、Trp、Gly或L...”(ix)特征:
(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第70位的Xaa是Asn、Leu、
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(A)名称/关键词:修饰位点
(B)位置:71
(D)其他信息:/注释=“在第71位的Xaa是Ala、Met、
Leu、Pro、Arg、Glu、Thr、Trp或
Asn;”(ix)特征:
(A)名称/关键词:修饰位点
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(D)其他信息:/注释=“在第72位的Xaa是Ser、Glu、
Met、Ala、His、Asn、Arg或Asp;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:73
(D)其他信息:/注释=“在第73位的Xaa是Ala、Glu、
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(A)名称/关键词:修饰位点
(B)位置:74
(D)其他信息:/注释=“在第74位的Xaa是Ile、Met、
Thr、Pro、Arg、Gly、Ala;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:75
(D)其他信息:/注释=“在第75位的Xaa是Glu、Lys、
Gly、Asp、Pro、Trp、Arg、Ser、Gln
或Leu;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:76
(D)其他信息:/注释=“在第76位的Xaa是Ser、Val、
Ala、Asn、Trp、Glu、Pro、Gly或A...”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:77
(D)其他信息:/注释=“在第77位的Xaa是Ile、Ser、
Arg、Thr或Leu;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:78
(D)其他信息:/注释=“在第78位的Xaa是Leu、Ala、
Ser、Glu、Phe、Gly或Arg;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:79
(D)其他信息:/注释=“在第79位的Xaa是Lys、Thr、
Asn、Met、Arg、Ile、Gly或Asp;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:80
(D)其他信息:/注释=“在第80位的Xaa是Asn、Trp、
Val、Gly、Thr、Leu、Glu或Arg;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:81
(D)其他信息:/注释=“在第81位的Xaa是Leu、Gln、
Gly、Ala、Trp、Arg、Val或Lys;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:82
(D)其他信息:/注释=“在第82位的Xaa是Leu、Gln、
Lys、Trp、Asp、Glu、Asn、His、Thr、
Ser、Ala、Tyr、Phe、Ile、Met或Val;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:83
(D)其他信息:/注释=“在第83位的Xaa是Pro、Ala、
Thr、Trp、Arg或Met;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:84
(D)其他信息:/注释=“在第84位的Xaa是Cys、Glu、
Gly、Arg、Met或Val;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:85
(D)其他信息:/注释=“在第85位的Xaa是Leu、Asn、
Val或Gln;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:86
(D)其他信息:/注释=“在第86位的Xaa是Pro、Cys、
Arg、Ala或Lys;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:87
(D)其他信息:/注释=“在第87位的Xaa是Leu、Ser、
Trp或Gly;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:88
(D)其他信息:/注释=“在第88位的Xaa是Ala、Lys、
Arg、Val或Trp;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:89
(D)其他信息:/注释=“在第89位的Xaa是Thr、Asp、
Cys、Leu、Val、Glu、His、Asn或S...”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:90
(D)其他信息:/注释=“在第90位的Xaa是Ala、Pro、
Ser、Thr、Gly、Asp、Ile或Met;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:91
(D)其他信息:/注释=“在第91位的Xaa是Ala、Pro、
Ser、Thr、Phe、Leu、Asp或His;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:92
(D)其他信息:/注释=“在第92位的Xaa是Pro、Phe、
Arg、Ser、Lys、His、Ala、Gly、Ile
或Leu;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:93
(D)其他信息:/注释=“在第93位的Xaa是Thr、Asp、
Ser、Asn、Pro、Ala、Leu或Arg;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:94
(D)其他信息:/注释=“在第94位的Xaa是Arg、Ile、
Ser、Glu、Leu、Val、Gln、Lys、His、
Ala或Pro;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:95
(D)其他信息:/注释=“在第95位的Xaa是His、Gln、
Pro、Arg、Val、Leu、Gly、Thr、Asn、
Lys、Ser、Ala、Trp、Phe、Ile或Tyr;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:96
(D)其他信息:/注释=“在第96位的Xaa是Pro、Lys、
Tyr、Gly、Ile或Thr;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:97
(D)其他信息:/注释=“在第97位的Xaa是Ile、Val、
Lys、Ala或Asn;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:98
(D)其他信息:/注释=“在第98位的Xaa是His、Ile、
Asn、Leu、Asp、Ala、Thr、Glu、Gln、
Ser、Phe、Met、Val、Lys、Arg、Tyr
或Pro;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:99
(D)其他信息:/注释=“在第99位的Xaa是Ile、Leu、
Arg、Asp、Val、Pro、Gln、Gly、Ser、
Phe或His;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:100
(D)其他信息:/注释=“在第100位的Xaa是Lys、Tyr、
Leu、His、Arg、Ile、Ser、Gln或...”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:101
(D)其他信息:/注释=“在第101位的Xaa是Asp、Pro、
Met、Lys、His、Thr、Val、Tyr、Glu、
Asn、Ser、Ala、Gly、Ile、Leu或Gln;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:102
(D)其他信息:/注释=“在第102位的Xaa是Gly、Leu、
Glu、Lys、Ser、Tyr或Pro;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:103
(D)其他信息:/注释=“在第103位的Xaa是Asp或Ser;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:104
(D)其他信息:/注释=“在第104位的Xaa是Trp、Val、
Cys、Tyr、Thr、Met、Pro、Leu、Gln、
Lys、Ala、Phe或Gly;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:105
(D)其他信息:/注释=“在第105位的Xaa是Asn、Pro、
Ala、Phe、Ser、Trp、Gln、Tyr、Leu、
Lys、Ile、Asp或His;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:106
(D)其他信息:/注释=“在第106位的Xaa是Glu、Ser、
Ala、Lys、Thr、Ile、Gly或Pro;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:108
(D)其他信息:/注释=“在第108位的Xaa是Arg、Lys、
Asp、Leu、Thr、Ile、Gln、His、Ser、
Ala或Pro;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:109
(D)其他信息:/注释=“在第109位的Xaa是Arg、Thr、
Pro、Glu、Tyr、Leu、Ser或Gly;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:110
(D)其他信息:/注释=“在第110位的Xaa是Lys、Ala、
Asn、Thr、Leu、Arg、Gln、His、Glu、
Ser或Trp;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:111
(D)其他信息:/注释=“在第111位的Xaa是Leu、Ile、
Arg、Asp或Met;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:112
(D)其他信息:/注释=“在第112位的Xaa是Thr、Val、
Gln、Tyr、Glu、His、Ser或Phe;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:113
(D)其他信息:/注释=“在第113位的Xaa是Phe、Ser、
Cys、His、Gly、Trp、Tyr、Asp、Lys、
Leu、Ile、Val或Asn;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:114
(D)其他信息:/注释=“在第114位的Xaa是Tyr、Cys、
His、Ser、Trp、Arg或Leu;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:115
(D)其他信息:/注释=“在第115位的Xaa是Leu、Asn、
Val、Pro、Arg、Ala、His、Thr、Trp
或Met;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:116
(D)其他信息:/注释=“在第116位的Xaa是Lys、Leu、
Pro、Thr、Met、Asp、Val、Glu、Arg、
Trp、Ser、Asn、His、Ala、Tyr、Phe、
Gln或Ile;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:117
(D)其他信息:/注释=“在第117位的Xaa是Thr、Ser、
Asn、Ile、Trp、Lys或Pro;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:118
(D)其他信息:/注释=“在第118位的Xaa是Leu、Ser、
Pro、Ala、Glu、Cys、Asp或Tyr;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:119
(D)其他信息:/注释=“在第119位的Xaa是Glu、Ser、
Lys、Pro、Leu、Thr、Tyr或Arg;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:120
(D)其他信息:/注释=“在第120位的Xaa是Asn、Ala、
Pro、Leu、His、Val或Gln;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:121
(D)其他信息:/注释=“在第121位的Xaa是Ala、Ser、
Ile、Asn、Pro、Lys、Asp或Gly;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:122
(D)其他信息:/注释=“在第122位的Xaa是Gln、Ser、
Met、Trp、Arg、Phe、Pro、His、Ile、
Tyr或Cys;”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:123
(D)其他信息:/注释=“在第123位的Xaa是Ala、Met、
Glu、His、Ser、Pro、Tyr或Leu;”(xi)序列描述:SEQ ID NO:2:
Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys
1 5 10 15
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75 80
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu
115 120 125
Ser Leu Ala Ile Phe
130(2)SEQ ID NO:3的信息:
(i)序列特性:
(A)长度:332个氨基酸
(B)类型:氨基酸
(C)链型:未知
(D)拓扑结构:未知
(ii)分子类型:蛋白
(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:112
(D)其他信息:/注释=“在112位缺失或是Leu、Ala、
Val、Ile、Pro、Phe、Trp或M...”
(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:113
(D)其他信息:/注释=“在113位缺失或是Pro、Phe、
Ala、Leu、Ile、Trp或Met;”
(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:114
(D)其他信息:/注释=“在114位缺失或是Pro、Phe、
Ala、Val、Leu、Ile、Trp或Met;”
(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:115
(D)其他信息:/注释=“在115位缺失或是Gln、Gly、
Ser、Thr、Tyr或Asn;”(xi)序列描述:SEQ ID NO:3:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp ser His Val Leu His ser Arg Leu ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Xaa
100 105 110Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg Arg Ala Pro Pro Thr Thr Ala145 150 155 160Val Pro Ser Arg Thr Ser Leu Val Leu Thr Leu Asn Glu Leu Pro Asn
165 170 175Arg Thr Ser Gly Leu Leu Glu Thr Asn Phe Thr Ala Ser Ala Arg Thr
180 185 190Thr Gly Ser Gly Leu Leu Lys Trp Gln Gln Gly Phe Arg Ala Lys Ile
195 200 205Pro Gly Leu Leu Asn Gln Thr Ser Arg Ser Leu Asp Gln Ile Pro Gly
210 215 220Tyr Leu Asn Arg Ile His Glu Leu Leu Asn Gly Thr Arg Gly Leu Phe225 230 235 240Pro Gly Pro Ser Arg Arg Thr Leu Gly Ala Pro Asp Ile Ser Ser Gly
245 250 255
Thr ser Asp Thr Gly Ser Leu Pro Pro Asn Leu Gln Pro Gly Tyr Ser
260 265 270
Pro Ser Pro Thr His Pro Pro Thr Gly Gln Tyr Thr Leu Phe Pro Leu
275 280 285
Pro Pro Thr Leu Pro Thr Pro Val Val Gln Leu His Pro Leu Leu Pro
290 295 300
Asp Pro Ser Ala Pro Thr Pro Thr Pro Thr Ser Pro Leu Leu Asn Thr
305 310 315 320
Ser Tyr Thr His Ser Gln Asn Leu Ser Gln Glu Gly
325 330(2)SEQ ID NO:4的信息:
(i)序列特性:
(A)长度:1个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(ix)特征
(A)名称/关键词:蛋白
(B)位置:1
(D)其他信息:/注释=“其中x=(glyglyglyser)n和其中n
是整数”
(xi)序列描述:SEQ ID NO:4:
Xaa
1(2)SEQ ID NO:5的信息:
(i)序列特性:
(A)长度:1个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(ix)特征
(A)名称/关键词:肽
(B)位置:1
(D)其他信息:/注释=“其中x=(glyglyglyglyser)n和n是
整数”
(xi)序列描述:SEQ ID NO:5:
Xaa
1(2)SEQ ID NO:6的信息:
(i)序列特性:
(A)长度:1个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(ix)特征
(A)名称/关键词:蛋白
(B)位置:1
(D)其他信息:/注释=“其中x=(glyglyglyglyglyser)n和n
是整数”
(xi)序列描述:SEQ ID NO:6:
Xaa
1(2)SEQ ID NO:7的信息:
(i)序列特性:
(A)长度:1个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(ix)特征
(A)名称/关键词:蛋白
(B)位置:1
(D)其他信息:/注释=“其中x=(glynser)n和n是整数“
(xi)序列描述:SEQ ID NO:7:
Xaa
1(2)SEQ ID NO:8的信息:
(i)序列特性:
(A)长度:1个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(ix)特征
(A)名称/关键词:蛋白
(B)位置:1
(D)其他信息:/注释=“其中x=(alaglyser)n和n是整数”
(xi)序列描述:SEQ ID NO:8:
Xaa
1(2)SEQ ID NO:9的信息:
(i)序列特性:
(A)长度:35个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白 (xi)序列描述:SEQ ID NO:9:
Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Ser
1 5 10 15
Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly
20 25 30
Gly Gly Ser
35(2)SEQ ID NO:10的信息:
(i)序列特性:
(A)长度:24个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:10:
Ile Ser Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Thr
1 5 10 15
Ser Lys Glu Ser His Lys Ser Pro
20(2)SEQ ID NO:11的信息:
(i)序列特性:
(A)长度:28个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:11:
Ile Glu Gly Arg Ile Ser Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn
1 5 10 15
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
20 25(2)SEQ ID NO:12的信息:
(i)序列特性:
(A)长度:4个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:12:
Gly Gly Gly Ser
1(2)SEQ ID NO:13的信息:
(i)序列特性:
(A)长度:45个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:13:
ACGTCCATGG CNTCNCCNGC NCCNCCTGCT TGTGCACTCC GAGTC
45(2)SEQ ID NO:14的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:14:
ATGCACGAAT TCCCTGACGC AGAGGGTGGA
30(2)SEQ ID NO:15的信息:
(i)序列特性:
(A)长度:33个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:15:TGACAAGCTT ACCTGACGCA GAGGGTGGAC CCT33(2)SEQ ID NO:16的信息:
(i)序列特性:
(A)长度:10个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:16:AATTCGGCAA10(2)SEQ ID NO:17的信息:
(i)序列特性:
(A)长度:10个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:17:CATGTTGCCG10(2)SEQ ID NO:18的信息:
(i)序列特性:
(A)长度:13个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:18:AATTCGGCGG CAA13(2)SEQ ID NO:19的信息:
(i)序列特性:
(A)长度:13个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:19:CATGTTGCCG CCG13(2)SEQ ID NO:20的信息:
(i)序列特性:
(A)长度:22个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:20:AATTCGGCGG CAACGGCGGC AA22(2)SEQ ID NO:21的信息:
(i)序列特性:
(A)长度:22个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:21:CATGTTGCCG CCGTTGCCGC CG22(2)SEQ ID NO:22的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:22:CGATCCATGG AGGTTCACCC TTTGCCT27(2)SEQ ID NO:23的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:23:GATCAAGCTT ATGGGCACTG GCTCAGTCT29(2)SEQ ID NO:24的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:24:CGATACATGT TGCCTACACC TGTCCTG27(2)SEQ ID NO:25的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:25:GATCAAGCTT AAGGGTGAAC CTCTGGGCA29(2)SEQ ID NO:26的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:26:CGATCCATGG TCCTGCTGCC TGCTGTG27(2)SEQ ID NO:27的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:27:GATCAAGCTT AAGGTGTAGG CAAAGGGTG29(2)SEQ ID NO:28的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:28:CGATCCATGG CTGTGGACTT TAGCTTGGGA30(2)SEQ ID NO:29的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:29:GATCAAGCTT AAGGCAGCAG GACAGGTGT29(2)SEQ ID NO:30的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:30:CGATCCATGG ACTTTAGCTTGGGAGAA27(2)SEQ ID NO:31的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:31:GATCAAGCTT ACACAGCAGG CAGCAGGAC29(2)SEQ ID NO:32的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:32:CGATCCATGG GAGAATGGAA AACCCAG27(2)SEQ ID NO:33的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:33:GATCAAGCTT ACAAGCTAAA GTCCACAGC29(2)SEQ ID NO:34的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:34:CGATCCATGG GACCCACTTG CCTCTCA27(2)SEQ ID NO:35的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:35:GATCAAGCTT ACAGTTGTCC CCGTGCTGC29(2)SEQ ID NO:36的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:36:CAGTCCATGG GAACCCAGCT TCCTCCA27(2)SEQ ID NO:37的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:37:GATCAAGCTT AAAGGAGGCT CTGCAGGGC29(2)SEQ ID NO:38的信息:
(i)序列特性:
(A)长度:27个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:38:CGATCCATGG GCAGGACCAC AGCTCAC27(2)SEQ ID NO:39的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:39:GATCAAGCTT ACTGTGGAGG AAGCTGGGTT30(2)SEQ ID NO:40的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:40:CGATCCATGG CTCACAAGGA TCCCAATGCC30(2)SEQ ID NO:41的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:41:GATCAAGCTT ATGTGGTCCT GCGCTGTGG29(2)SEQ ID NO:42的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:42:CGATCCATGG ATCCCAATGC CATCTTCCTG30(2)SEQ ID NO:43的信息:
(i)序列特性:
(A)长度:29个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:43:GATCAAGCTT ACTTGTGAGC TGTGGTCCT29(2)SEQ ID NO:44的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:44:CGATCCATGG CCATCTTCCT GAGCTTCCAA30(2)SEQ ID NO:45的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:45:GATCAAGCTT AATTGGGATC CTTGTGAGCT GT32(2)SEQ ID NO:46的信息:
(i)序列特性:
(A)长度:83个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:46:AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT60ACGTAGAGGG CGGTGGAGGC TCC83(2)SEQ ID NO:47的信息:
(i)序列特性:
(A)长度:83个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:47:CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AAGGTTTTCA60GATAGAAGGT CAGTTTACGA CGG83(2)SEQ ID NO:48的信息:
(i)序列特性:
(A)长度:59个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:48:GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTAACTGCTC TATAATGAT59(2)SEQ ID NO:49的信息:
(i)序列特性:
(A)长度:56个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:49:CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC CTGCGCTTGC TCAAGG56(2)SEQ ID NO:50的信息:
(i)序列特性:
(A)长度:80个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:50:GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTGGCGGTGG CAGCGGCGGC60GGTTCTAACT GCTCTATAAT80(2)SEQ ID NO:51的信息:
(i)序列特性:
(A)长度:80个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:51:CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC GCCAGAGCCA CCACCCTGTT60GTTCCTGCGC TTGCTCAAGG80(2)SEQ ID NO:52的信息:
(i)序列特性:
(A)长度:30个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:52:GATCGACCAT GGCTCTGGAC CCGAACAACC30(2)SEQ ID NO:53的信息:
(i)序列特性:
(A)长度:28个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:53:CTCGATTACGTACAAAGGTG CAGGTGGT28(2)SEQ ID NO:54的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:54:GATCGACCAT GGCTAATGCA TCAGGTATTG AG32(2)SEQ ID NO:55的信息:
(i)序列特性:
(A)长度:28个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:55:CTCGATTACG TATTCTAAGT TCTTGACA28(2)SEQ ID NO:56的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:56:GATCGACCAT GGCTGCACCC TCTCGACATC CA32(2)SEQ ID NO:57的信息:
(i)序列特性:
(A)长度:28个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:57:CTCGATTACG TAGGCCGTGG CAGAGGGC28(2)SEQ ID NO:58的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:58:GATCGACCAT GGCTGCAGGT GACTGGCAAG AA32(2)SEQ ID NO:59的信息:
(i)序列特性:
(A)长度:28个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:59:CTCGATTACG TACTTGATGA TGATTGGA28(2)SEQ ID NO:60的信息:
(i)序列特性:
(A)长度:54个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:60:GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG CTGCGCAAGG TGGCGTAGAA CGCG54(2)SEQ ID NO:61的信息:
(i)序列特性:
(A)长度:54个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:61:CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAG54(2)SEQ ID NO:62的信息:
(i)序列特性:
(A)长度:18个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:62:GGGCTGCGCA AGGTGGCG18(2)SEQ ID NO:63的信息:
(i)序列特性:
(A)长度:21个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:63ACACCATTGG GCCCTGCCAG C21(2)SEQ ID NO:64的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:64:GATCGACCAT GGCTTACAAG CTGTGCCACC CC32(2)SEQ ID NO:65的信息:
(i)序列特性:
(A)长度:36个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:65:CGATCGAAGC TTATTAGGTG GCACACAGCT TCTCCT36(2)SEQ ID NO:66的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:66:GATCGACCAT GGCTCCCGAG TTGGGTCCCA CC32(2)SEQ ID NO:67的信息:
(i)序列特性:
(A)长度:36个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:67:CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT36(2)SEQ ID NO:68的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:68:
GATCGACCAT GGCTATGGCC CCTGCCCTGC AG
32(2)SEQ ID NO:69的信息:
(i)序列特性:
(A)长度:36个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:69:CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT36(2)SEQ ID NO:70的信息:
(i)序列特性:
(A)长度:32个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:70:GATCGACCAT GGCTACCCAG GGTGCCATGC CG32(2)SEO ID NO:71的信息:
(i)序列特性:
(A)长度:36个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:71:CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA36(2)SEQ ID NO:72的信息:
(i)序列特性:
(A)长度:36个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:72:CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA36(2)SEQ ID NO:73的信息:
(i)序列特性:
(A)长度:36个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc“DNA(合成物)”
(xi)序列描述:SEQ ID NO:73:CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC36(2)SEQ ID NO:74的信息:
(i)序列特性:
(A)长度:21个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:74:GTAGAGGGCG GTGGAGGCTC C21(2)SEQ ID NO:75的信息:
(i)序列特性:
(A)长度:25个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:75:CCGGGGAGCC TCCACCGCCC TCTAC25(2)SEQ ID NO:76的信息:
(i)序列特性:
(A)长度:53个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:76:TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT GTCTACACCA TTG53(2)SEQ ID NO:77的信息:
(i)序列特性:
(A)长度:53个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:77:CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA AGGTGGCGTA GAA53(2)SEQ ID NO:78的信息:
(i)序列特性:
(A)长度:439个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:78:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGT439(2)SEQ ID NO:79的信息:
(i)序列特性:
(A)长度:465个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:79:TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTGCTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTTCTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTC465(2)SEQ ID NO:80的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:80:TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CAACATGGCG480TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT540GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG600CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA660CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA720CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC780CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGGGCAGGA CCACAGCTCA CAAGGATCCC840AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT900GTAGGAGGGT CCACCCTCTG CGTCAGG927(2)SEQ ID NO:81的信息:
(i)序列特性:
(A)长度:936个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:81:TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCAA CATGGCGTCT480CCCGCTCCGC CTGCTTGTGA CCTCCGAGTC CTCAGTAAAC TGCTTCGTGA CTCCCATGTC540CTTCACAGCA GACTGAGCCA GTGCCCAGAG GTTCACCCTT TGCCTACACC TGTCCTGCTG600CCTGCTGTGG ACTTTAGCTT GGGAGAATGG AAAACCCAGA TGGAGGAGAC CAAGGCACAG660GACATTCTGG GAGCAGTGAC CCTTCTGCTG GAGGGAGTGATGGCAGCACG GGGACAACTG720GGACCCACTT GCCTCTCATC CCTCCTGGGG CAGCTTTCTG GACAGGTCCG TCTCCTCCTT780GGGGCCCTGC AGAGCCTCCT TGGAACCCAG CTTCCTCCAC AGGGCAGGAC CACAGCTCAC840AAGGATCCCA ATGCCATCTT CCTGAGCTTC CAACACCTGC TCCGAGGAAA GGTGCGTTTC900CTGATGCTTG TAGGAGGGTC CACCCTCTGC GTCAGG936(2)SEQ ID NO:82的信息:
(i)序列特性:
(A)长度:939个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:82:TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CAACATGGCG480TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT540GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG600CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA660CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA720CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC780 CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT840CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT900TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGG939(2)SEQ ID NO:83的信息:
(i)序列特性:
(A)长度:948个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:83:TCCCCAGCGC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CAACGGCGGC480AACATGGCGT CCCCAGCGCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGT540GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TTTGCCTACA600 CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAAT GGAAAACCCA GATGGAGGAG660ACCAAGGCAC AGGACATTCT GGGAGCAGTG ACCCTTCTGC TGGAGGGAGT GATGGCAGCA720CGGGGACAAC TGGGACCCAC TTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC780CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC ACAGGGCAGG840ACCACAGCTC ACAAGGATCC CAATGCCATC TTCCTGAGCT TCCAACACCT GCTCCGAGGA900AAGGTGCGTT TCCTGATGCT TGTAGGAGGG TCCACCCTCT GCGTCAGG948(2)SEQ ID NO:84的信息:
(i)序列特性:
(A)长度:688个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:84:CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC60ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA120CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC180AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC240CTCTCGACAT CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC300GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTAACTGCTC360TATAATGATC GATGAAATTA TACATCACTT AAAGAGACCA CCTGCACCTT TGCTGGACCC420 GAACAACCTC AATGACGAAG ACGTCTCTAT CCTGATGGAC CGAAACCTTC GACTTCCAAA480CCTGGAGAGC TTCGTAAGGG CTGTCAAGAA CTTAGAAAAT GCATCAGGTA TTGAGGCAAT540TCTTCGTAAT CTCCAACCAT GTCTGCCCTC TGCCACGGCC GCACCCTCTC GACATCCAAT600CATCATCAAG GCAGGTGACT GGCAAGAATT CCGGGAAAAA CTGACGTTCT ATCTGGTTAC660CCTTGAGCAA GCGCAGGAAC AACAGTAC688(2)SEQ ID NO:85的信息:
(i)序列特性:
(A)长度:712个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:85:CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC60ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA120CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC180AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC240CTCTCGACAT CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC300GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTGGCGGTGG360CAGCGGCGGC GGTTCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG420 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT480GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA540AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC600GGCCGCACCC TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA660AAAACTGACG TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT AC712(2)SEQ ID NO:86的信息:
(i)序列特性:
(A)长度:975个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:86:ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC60CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA120GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC180TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAAACTGACG240TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT300ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GTACGTAGAG360GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT420CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC480 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC540CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC600TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA660GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG720CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG780CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG840CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC900GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC960CTGCAGCCCT AATAA975(2)SEQ ID NO:87的信息:
(i)序列特性:
(A)长度:975个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:87:ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC60CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA120GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC180TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG240 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT300ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GTACGTAGAG360GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT420CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC480GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC540CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC600TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA660GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG720CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG780CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG840CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC900GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC960CTGCAGCCCT AATAA975(2)SEQ ID NO:88的信息:
(i)序列特性:
(A)长度:975个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:88: ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG60GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC120TCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT180TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT240CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT300ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CTACGTAGAG360GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT420CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC480GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC540CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC600TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA660GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG720CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG780CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG840CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC900GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC960CTGCAGCCCT AATAA975(2)SEQ ID NO:89的信息:
(i)序列特性:
(A)长度:975个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:89:ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT60GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CGATGAAATT120ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT CAATGACGAA180GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG240GCTGTCAAGA ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA300TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GTACGTAGAG360GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT420CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC480GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC540CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC600TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA660GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG720CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG780CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG840 CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC900GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC960CTGCAGCCCT AATAA975(2)SEQ ID NO:90的信息:
(i)序列特性:
(A)长度:999个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:90:ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC60CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA120GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC180TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG240TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TGGCGGTGGC300AGCGGCGGCG GTTCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA CTTAAAGAGA360CCACCTGCAC CTTTGTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA420ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT480ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG540 GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG600CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG660AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG720TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG780AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC840CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC900ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG960GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA999(2)SEQ ID NO:91的信息:
(i)序列特性:
(A)长度:999个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:91:ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG TCTGCCCTCT60GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG CAGGTGACTG GCAAGAATTC120CGGGAAAAAC TGACGTTCTA TCTGGTTACC CTTGAGCAAG CGCAGGAACA ACAGGGTGGT180GGCTCTGGCG GTGGCAGCGG CGGCGGTTCT AACTGCTCTA TAATGATCGA TGAAATTATA240 CATCACTTAA AGAGACCACC TGCACCTTTG CTGGACCCGA ACAACCTCAA TGACGAAGAC300GTCTCTATCC TGATGGACCG AAACCTTCGA CTTCCAAACC TGGAGAGCTT CGTAAGGGCT360GTCAAGAACT TAGAATACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA420ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT480ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG540GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG600CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG660AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG720TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG780AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC840CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC900ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG960GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA999(2)SEQ ID NO:92的信息:
(i)序列特性:
(A)长度:999个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:92: ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG60GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC120TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC TGCTCTATAA TGATCGATGA AATTATACAT180CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC240TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC300AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG360CCCTCTGCCA CGGCCTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA420ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT480ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG540GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG600CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG660AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG720TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG780AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC840CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC900ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG960GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA999(2)SEQ ID NO:93的信息:
(i)序列特性:
(A)长度:999个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:93ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT60GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC120TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC ACCTTTGCTG180GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA CCTTCGACTT240CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG300GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT360CCAATCATCA TCAAGTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA420ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT480ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG540GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG600CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG660AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG720TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG780AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC840 CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC900ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG960GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA999(2)SEQ ID NO:94的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:94:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT ACAAGCTGTG CCACCCCGAG420GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC480AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC540CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA600 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA660ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TGCTTTCCAG720CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GGTGTCGTAC780CGCGTTCTAC GCCACCTTGC GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG840CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG900CTGTGTGCCA CCTAATAA918(2)SEQ ID NO:95的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:95:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420 TCTCATAAAT CTCCAAACAT GGCTTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC480GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG540CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG600GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC660GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG720CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG780GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC840CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG900CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA960TAA963(2)SEQ ID NO:96的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:96:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180 GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TCCCACCTTG420GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA480CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT540TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTTT CCTGGAGGTG600TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG CTCTCAGAGC660TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG GCGATGGCGC AGCGCTCCAG720GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCTGCTCGGACAC780TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCTGCAGCTGGCA840GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG900GAAGGGATAT CCTAATAA918(2)SEQ ID NO:97的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:97: ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG480GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT540GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA600GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA660CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT720TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC780ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC840TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA900CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCTAA960TAA963(2)SEQ ID NO:98的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:98:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA TGGCCCCTGC CCTGCAGCCC420ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG480GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG540CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG600AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG660TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG720AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC780CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC840 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG900GAAGAACTGG GATAATAA918(2)SEQ ID NO:99的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:99:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG480CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG540CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC600 TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA GATCCAGGGC660GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CCCCGAGGAG720CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC780CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG840GGGCTCCTGC AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG900CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA ACTGGGATAA960TAA963(2)SEQ ID NO:100的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:100:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CCCAGGGTGC CATGCCGGCC420TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC480TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCTCTGG CGGCTCTGGC540GGCTCTCAGA GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GGGCGATGGC600GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTG660CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC720CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA CCAGGGGCTC780CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG840GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT900GCCCTGCAGC CCTAATAA918(2)SEQ ID NO:101的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:101:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120 CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC600CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG660AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCTCGGACACTCT720CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC780TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA840GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGTCGCCGACTTT900GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA960TAA963(2)SEQ ID NO:102的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:102:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT CTGCTTTCCA GCGCCGGGCA420GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA480CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT540TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC600ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC660TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA720CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC780GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC840TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG900CCGGCCTTCG CCTAATAA918(2)SEQ ID NO:103的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:103:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTTCTGCT TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT480GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG540CCCTCTGGCG GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA600AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC660CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC720TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT780 TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC840TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA900GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTAA960TAA963(2)SEQ ID NO:104的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:104:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT ACAAGCTGTG CCACCCCGAG420GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC480AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC540 CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA600CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA660ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TGCTTTCCAG720CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GGTGTCGTAC780CGCGTTCTAC GCCACCTTGC GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG840AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC900CAGGAGAAGC TGTGTGCCAC CTAATAA927(2)SEQ ID NO:105的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:105:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC480GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG540CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG600GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC660GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG720CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG780GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC840CTTGCGCAGC CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG900TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT960GCCACCTAAT AA972(2)SEQ ID NO:106的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:106:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60 CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TCCCACCTTG420GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA480CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT540TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG600TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT TGGGCCCTGC CAGCTCCCTG660CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA720GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG780CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG840CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG900CAGGCCCTGG AAGGGATATC CTAATAA927(2)SEQ ID NO:107的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:107:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG480GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT540GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA600GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA660CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG720CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG780CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG840GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC900 TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CCTGGAAGGG960ATATCCTAAT AA972(2)SEQ ID NO:108的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:108:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA TGGCCCCTGC CCTGCAGCCC420ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG480GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG540CAGCCCACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA600 GAGCAAGTGA GAAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC660TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG720GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC780CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG840TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG900CAGCAGATGG AAGAACTGGG ATAATAA927(2)SEQ ID NO:109的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:109:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360 TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG480CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG540CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CACACCATTG600GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG660ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC720CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC780TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC840CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG900GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA960CTGGGATAAT AA972(2)SEQ ID NO:110的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:110:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120 CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CCCAGGGTGC CATGCCGGCC420TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC480TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCACACC ATTGGGCCCT540GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AAAGATCCAG600GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CCACCCCGAG660GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC720AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC780CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA840CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA900ATGGCCCCTG CCCTGCAGCC CTAATAA927(2)SEQ ID NO:111的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:111:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC600CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TGGCGCAGCG660CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC720GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG780CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG840GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC900GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG960CAGCCCTAAT AA972(2)SEQ ID NO:112的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:112:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT CTGCTTTCCA GCGCCGGGCA420GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA480CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG540CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG600CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG660GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC720TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CCTGGAAGGG780 ATATCCCCCG AGTTGGGTCC CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC840ACCACCATCT GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG900(2)SEQ ID NO:113的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:113:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTTCTGCT TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT480GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG540CCCACACCAT TGGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG600 CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC660AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT720CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG CCAACTCCAT780AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG AAGGGATATC CCCCGAGTTG840GGTCCCACCT TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CATCTGGCAG900CAGATGGAAG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC CATGCCGGCC960TTCGCCTAAT AA972(2)SEQ ID NO:114的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:114:ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTAAT GGACAATAAC120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC300 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC600CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG660AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT720CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC780TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA840GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT900GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA960TAA963(2)SEQ ID NO:115的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:115:ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC240ACGCGACATC CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC600CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TGGCGCAGCG660CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC720GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG780CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG840GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC900GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG960CAGCCCTAAT AA972(2)SEQ ID NO:116的信息:
(i)序列特性:
(A)长度:963个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:116:ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC240ACGCGACATC CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC600CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG660AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT720 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC780TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA840GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT900GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA960TAA963(2)SEQ ID NO:117的信息:
(i)序列特性:
(A)长度:972个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:117:ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTAAT GGACAATAAC120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420 TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC600CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TGGCGCAGCG660CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC720GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG780CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG840GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC900GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG960CAGCCCTAAT AA972(2)SEQ ID NO:118的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:118:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180 ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA GGTTCACCCT TTGCCTACAC CTGTCCTGCT GCCTGCTGTG480GACTTTAGCT TGGGAGAATG GAAAACCCAG ATGGAGGAGA CCAAGGCACA GGACATTCTG540GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG ATGGCAGCAC GGGGACAACT GGGACCCACT600TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT GGACAGGTCC GTCTCCTCCT TGGGGCCCTG660CAGAGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CAAGGATCCC720AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT780GTAGGAGGGT CCACCCTCTG CGTCAGGGAA TTCGGCGGCA ACATGGCGTC TCCCGCTCCG840CCTGCTTGTG ACCTCCGAGT CCTCAGTAAA CTGCTTCGTG ACTCCCATGT CCTTCACAGC900AGACTGAGCC AGTGCCCA918(2)SEQ ID NO:119的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:119: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TICTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG480GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AGCAGTGACC540CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CCTCTCATCC600CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT660GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC720CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCC780ACCCTCTGCG TCAGGGAATT CGGCGGCAAC ATGGCGTCTC CCGCTCCGCC TGCTTGTGAC840CTCCGAGTCC TCAGTAAACT GCTTCGTGAC TCCCATGTCC TTCACAGCAG ACTGAGCCAG900TGCCCAGAGG TTCACCCT918(2)SEQ ID NO:120的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:120:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA480ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG540GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CCTGGGGCAG600CTTTCTGGAC AGGTCCGTCI CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AACCCAGCTT660CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GAGCTTCCAA720CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC780AGGGAATTCG GCGGCAACAT GGCGTCTCCC GCTCCGCCTG CTTGTGACCT CCGAGTCCTC840AGTAAACTGC TTCGTGACTC CCATGTCCTT CACAGCAGAC TGAGCCAGTG CCCAGAGGTT900CACCCTTTGC CTACACCT918(2)SEQ ID NO:121的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:121:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG480GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA540GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG600GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC660AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA720GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC780 GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT840CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT900ACACCTGTCC TGCTGCCT918(2)SEQ ID NO:122的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:122:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC480AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG540 GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT600CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC660ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG720GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC780ATGGCGTCTC CCGCTCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACT GCTTCGTGAC840TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGG TTCACCCTTT GCCTACACCT900GTCCTGCTGC CTGCTGTG918(2)SEQ ID NO:123的信息:
(i)序列特性:
(A)长度:907个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:123:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCGGTTAC CCTTGAGCAA GCGCAGGAAC AACAGTACGT AGAGGGCGGT GGAGGCTCCC360 CGGGGAACCG TCTGGTCCAA TCTCTACTAT CAACCCGTCT CCTCCGTCTA AAGAATCTCA420TAAACTCCAA ACATGGGAGA ATGGAAAACC CAGATGGAGG AGACCAAGGC ACAGGACATT480CTGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA540CTTGCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCC TTGGGGCCCT600GCAGGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CAAGGATCCC660AATGCATCTT CCTGAGCTTC CAACACCTGC TCCGAGGAAA GGTGCGTTTC CTGATGCTTG720TAGGGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC ATGGCGTCTC CCGCTCCGCC780TGCTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TCACAGCAGA840CTGACCAGTG CCCAGAGGTT CACCCTTTGC CTACACCTGT CCTGCTGCCT GCTGTGGACT900TTAGTTG907(2)SEQ ID NO:124的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:124:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180 ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GCTTTCTGGA480CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TCCTCCACAG540GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA ACACCTGCTC600CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CAGGGAATTC660GGCGGCAACA TGGCGTCTCC CGCTCCGCCT GCTTGTGACC TCCGAGTCCT CAGTAAACTG720CTTCGTGACT CCCATGTCCT TCACAGCAGA CTGAGCCAGT GCCCAGAGGT TCACCCTTTG780CCTACACCTG TCCTGCTGCC TGCTGTGGAC TTTAGCTTGG GAGAATGGAA AACCCAGATG840GAGGAGACCA AGGCACAGGA CATTCTGGGA GCAGTGACCC TTCTGCTGGA GGGAGTGATG900GCAGCACGGG GACAACTG918(2)SEQ ID NO:125的信息:
(i)序列特性:
(A)长度:848个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:125: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG480GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG540ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACAT GGCGTCTCCC600GCTCCGCCTG CTTGTGACCT CCGAGTCCTC AGTAAACTGC TTCGTGACTC CCATGTCCTT660CACAGCAGAC TGAGCCAGTG CCCAGAGGTT CACCCTTTGC CTACACCTGT CCTGCTGCCT720GCTGTGGACT TTAGCTTGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GGCACAGGAC780ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG ACAACTGGGA840CCCACTTG848(2)SEQ ID NO:126的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:126:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG480AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AGGGTCCACC540CTCTGCGTCA GGGAATTCGG CGGCAACATG GCGTCTCCCG CTCCGCCTGC TTGTGACCTC600CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GAGCCAGTGC660CCAGAGGTTC ACCCTTTGCC TACACCTGTC CTGCTGCCTG CTGTGGACTT TAGCTTGGGA720GAATGGAAAA CCCAGATGGA GGAGACCAAG GCACAGGACA TTCTGGGAGC AGTGACCCTT780CTGCTGGAGG GAGTGATGGC AGCACGGGGA CAACTGGGAC CCACTTGCCT CTCATCCCTC840CTGGGGCAGC TTTCTGGACA GGTCCGTCTC CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA900ACCCAGCTTC CTCCACAG918(2)SEQ ID NO:127的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:127:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CTTCCAACAC480CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CTGCGTCAGG540GAATTCGGCG GCAACATGGC GTCTCCCGCT CCGCCTGCTT GTGACCTCCG AGTCCTCAGT600AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC660CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC720CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GCTGGAGGGA780 GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GGGGCAGCTT840TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT900CCACAGGGCA GGACCACA918(2)SEQ ID NO:128的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:128:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA480GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC540GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT600 CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT660ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG720GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA780GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG840GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC900AGGACCACAG CTCACAAG918(2)SEQ ID NO:129的信息:
(i)序列特性:
(A)长度:918个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:129:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360 CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG480CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CGGCAACATG540GCGTCTCCCG CTCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC600CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC660CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA CCCAGATGGA GGAGACCAAG720GCACAGGACA TTCTGGGAGC AGTGACCCTT CTGCTGGAGG GAGTGATGGC AGCACGGGGA780CAACTGGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA GGTCCGTCTC840CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA ACCCAGCTTC CTCCACAGGG CAGGACCACA900GCTCACAAGG ATCCCAAT918(2)SEQ ID NO:130的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:130:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180 ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCCGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA GGTTCACCCT TTGCCTACAC CTGTCCTGCT GCCTGCTGTG480GACTTTAGCT TGGGAGAATG GAAAACCCAG ATGGAGGAGA CCAAGGCACA GGACATTCTG540GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG ATGGCAGCAC GGGGACAACT GGGACCCACT600TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT GGACAGGTCC GTCTCCTCCT TGGGGCCCTG660CAGAGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CAAGGATCCC720AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT780GTAGGAGGGT CCACCCTCTG CGTCAGGGAA TTCGGCAACA TGGCGTCTCC CGCTCCGCCT840GCTTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TCACAGCAGA900CTGAGCCAGT GCCCA915(2)SEQ ID NO:131的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:131: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG480GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AGCAGTGACC540CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CCTCTCATCC600CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT660GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC720CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCC780ACCCTCTGCG TCAGGGAATT CGGCAACATG GCGTCTCCCG CTCCGCCTGC TTGTGACCTC840CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GAGCCAGTGC900CCAGAGGTTC ACCCT915(2)SEQ ID NO:132的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:132:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA480ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG540GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CCTGGGGCAG600CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AACCCAGCTT660CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GAGCTTCCAA720CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC780AGGGAATTCG GCAACATGGC GTCTCCCGCT CCGCCTGCTT GTGACCTCCG AGTCCTCAGT840AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC900CCTTTGCCTA CACCT915(2)SEQ ID NO:133的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:133:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG480GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA540GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG600GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC660AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA720GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC780 AACATGGCGT CTCCCGCTCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGT840GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TTTGCCTACA900CCTGTCCTGC TGCCT915(2)SEQ ID NO:134的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:134:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC480AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG540GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT600 CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC660ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG720GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CGGCAACATG780GCGTCTCCCG CTCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC840CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC900CTGCTGCCTG CTGTG915(2)SEQ ID NO:135的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:135:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420 CATAAATCTC CAAACATGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GGCACAGGAC480ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG ACAACTGGGA540CCCACTTGCC TCTCATCCCT CCTGGGGCAG CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG600GCCCTGCAGA GCCTCCTTGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG660GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG720ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCAACATGGC GTCTCCCGCT780CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TGTCCTTCAC840AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA CACCTGTCCT GCTGCCTGCT900GTGGACTTTA GCTTG915(2)SEQ ID NO:136的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:136:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240 CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GCTTTCTGGA480CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TCCTCCACAG540GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA ACACCTGCTC600CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CAGGGAATTC660GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT720CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT780ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG840GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA900GCACGGGGAC AACTG915(2)SEQ ID NO:137的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:137: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG480GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG540ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCAACATGGC GTCTCCCGCT600CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TGTCCTTCAC660AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA CACCTGTCCT GCTGCCTGCT720GTGGACTTTA GCTTGGGAGA ATGGAAAACC CAGATGGAGG AGACCAAGGC ACAGGACATT780CTGGGAGCAG TGACCCTTCT GCTGGAGGGA GTGATGGCAG CACGGGGACA ACTGGGACCC840ACTTGCCTCT CATCCCTCCT GGGGCAGCTT TCTGGACAGG TCCGTCTCCT CCTTGGGGCC900CTGCAGAGCC TCCTT915(2)SEQ ID NO:138的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:138:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG480AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AGGGTCCACC540CTCTGCGTCA GGGAATTCGG CAACATGGCG TCTCCCGCTC CGCCTGCTTG TGACCTCCGA600GTCCTCAGTA AACTGCTTCG TGACTCCCAT GTCCTTCACA GCAGACTGAG CCAGTGCCCA660GAGGTTCACC CTTTGCCTAC ACCTGTCCTG CTGCCTGCTG TGGACTTTAG CTTGGGAGAA720TGGAAAACCC AGATGGAGGA GACCAAGGCA CAGGACATTC TGGGAGCAGT GACCCTTCTG780CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA CTTGCCTCTC ATCCCTCCTG840 GGGCAGCTTT CTGGACAGGT CCGTCTCCTC CTTGGGGCCC TGCAGAGCCT CCTTGGAACC900CAGCTTCCTC CACAG915(2)SEQ ID NO:139的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:139:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CTTCCAACAC480CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CTGCGTCAGG540GAATTCGGCA ACATGGCGTC TCCCGCTCCG CCTGCTTGTG ACCTCCGAGT CCTCAGTAAA600
CTGCTTCGTG ACTCCCATGT CCTTCACAGC AGACTGAGCC AGTGCCCAGA GGTTCACCCT
660
TTGCCTACAC CTGTCCTGCT GCCTGCTGTG GACTTTAGCT TGGGAGAATG GAAAACCCAG
720
ATGGAGGAGA CCAAGGCACA GGACATTCTG GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG
780
ATGGCAGCAC GGGGACAACT GGGACCCACT TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT
840
GGACAGGTCC GTCTCCTCCT TGGGGCCCTG CAGAGCCTCC TTGGAACCCA GCTTCCTCCA
900
CAGGGCAGGA CCACA
915(2)SEQ ID NO:140的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:140:
GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT
60
TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT
120
CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT
180
ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT
240
CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC
300
TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC
360
CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT
420
CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA
480
GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC
540
AACATGGCGT CTCCCGCTCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGT
600
GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TTTGCCTACA
660
CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAAT GGAAAACCCA GATGGAGGAG
720
ACCAAGGCAC AGGACATTCT GGGAGCAGTG ACCCTTCTGC TGGAGGGAGT GATGGCAGCA
780
CGGGGACAAC TGGGACCCAC TTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC
840
CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC ACAGGGCAGG
900
ACCACAGCTC ACAAG
915(2)SEQ ID NO:141的信息:
(i)序列特性:
(A)长度:915个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:141:
GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT
60
TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT
120
CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT
180
ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT
240
CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC
300
TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC
360
CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT
420
CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG
480
CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CAACATGGCG
540
TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT
600
GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG
660
CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA
720
CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA
780
CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC
840
CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT
900
CACAAGGATC CCAAT
915(2)SEQ ID NO:142的信息:
(i)序列特性:
(A)长度:921个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:142: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120GACTTCCAAA CCTGGAGAGC TTCGTAAGGG CTGTCAAGAA CTTAGAAAAT GCATCAGGTA180TGAGGCAATT CTTCGTAATC TCCAACCATG TCTGCCCTCT GCCACGGCCG CACCCTCTCG240CATCCAATCA TCATCAAGGC AGGTGACTGG CAAGAATTCC GGGAAAAACT GACGTTCTAT300TGGTTACCCT TGAGCAAGCG CAGGAACAAC AGTACGTAGA GGGCGGTGGA GGCTCCCCGG360TAACCGTCTG GTCCAATCTC TACTATCAAC CCGTCTCCTC CGTCTAAAGA ATCTCATAAA420TCTCCAAACA TGGAGGTTCA CCCTTTGCCT ACACCTGTCC TGCTGCCTGC TGTGGACTTT480AGCTTGGGAG AATGGAAAAC CCAGATGGAG GAGACCAAGG CACAGGACAT TCTGGGAGCA540GTGACCCTTC TGCTGGAGGG AGTGATGGCA GCACGGGGAC AACTGGGACC CACTTGCCTC600TCATCCCTCC TGGGGCAGCT TTCTGGACAG GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC660CTCCTTGGAA CCCAGCTTCC TCCACAGGGC AGGACCACAG CTCACAAGGA TCCCAATGCC720ATCTTCCTGA GCTTCCAACA CCTGCTCCGA GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA780GGGTCCACCC TCTGCGTCAG GGAATTCGGC GGCAACGGCG GCAACATGGC GTCCCCAGCG840CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TGTCCTTCAC900AGCAGACTGA GCCAGTGCCC A921(2)SEQ ID NO:143的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:143:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG480GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AGCAGTGACC540CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CCTCTCATCC600CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT660GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC720CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCC780ACCCTCTGCG TCAGGGAATT CGGCGGCAAC GGCGGCAACA TGGCGTCCCC AGCGCCGCCT840GCTTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TCACAGCAGA900CTGAGCCAGT GCCCAGAGGT TCACCCT927(2)SEQ ID NO:144的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:144:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA480ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG540GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CCTGGGGCAG600CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AACCCAGCTT660CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GAGCTTCCAA720 CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC780AGGGAATTCG GCGGCAACGG CGGCAACATG GCGTCCCCAG CGCCGCCTGC TTGTGACCTC840CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GAGCCAGTGC900CCAGAGGTTC ACCCTTTGCC TACACCT927(2)SEQ ID NO:145的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:145:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG480 GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA540GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG600GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC660AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA720GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC780GGCAACGGCG GCAACATGGC GTCCCCAGCG CCGCCTGCTT GTGACCTCCG AGTCCTCAGT840AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC900CCTTTGCCTA CACCTGTCCT GCTGCCT927(2)SEQ ID NO:146的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:146:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240 CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC480AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG540GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT600CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC660ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG720GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC780GGCGGCAACA TGGCGTCCCC AGCGCCGCCT GCTTGTGACC TCCGAGTCCT CAGTAAACTG840CTTCGTGACT CCCATGTCCT TCACAGCAGA CTGAGCCAGT GCCCAGAGGT TCACCCTTTG900CCTACACCTG TCCTGCTGCC TGCTGTG927(2)SEQ ID NO:147的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:147: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTCGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GGCACAGGAC480ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG ACAACTGGGA540CCCACTTGCC TCTCATCCCT CCTGGGGCAG CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG600GCCCTGCAGA GCCTCCTTGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG660GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG720ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACGG CGGCAACATG780GCGTCCCCAG CGCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC840CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC900CTGCTGCCTG CTGTGGACTT TAGCTTG927(2)SEQ ID NO:148的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:148:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GCTTTCTGGA480CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TCCTCCACAG540GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA ACACCTGCTC600CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CAGGGAATTC660GGCGGCAACG GCGGCAACAT GGCGTCCCCA GCGCCGCCTG CTTGTGACCT CCGAGTCCTC720AGTAAACTGC TTCGTGACTC CCATGTCCTT CACAGCAGAC TGAGCCAGTG CCCAGAGGTT780CACCCTTTGC CTACACCTGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA840ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG900GGAGTGATGG CAGCACGGGG ACAACTG927(2)SEQ ID NO:149的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:149:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG480GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG540ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACGG CGGCAACATG600GCGTCCCCAG CGCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC660CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC720 CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA CCCAGATGGA GGAGACCAAG780GCACAGGACA TTCTGGGAGC AGTGACCCTT CTGCTGGAGG GAGTGATGGC AGCACGGGGA840CAACTGGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA GGTCCGTCTC900CTCCTTGGGG CCCTGCAGAG CCTCCTT927(2)SEQ ID NO:150的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:150:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG480 AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AGGGTCCACC540CTCTGCGTCA GGGAATTCGG CGGCAACGGC GGCAACATGG CGTCCCCAGC GCCGCCTGCT600TGTGACCTCC GAGTCCTCAG TAAACTGCTT CGTGACTCCC ATGTCCTTCA CAGCAGACTG660AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT ACACCTGTCC TGCTGCCTGC TGTGGACTTT720AGCTTGGGAG AATGGAAAAC CCAGATGGAG GAGACCAAGG CACAGGACAT TCTGGGAGCA780GTGACCCTTC TGCTGGAGGG AGTGATGGCA GCACGGGGAC AACTGGGACC CACTTGCCTC840TCATCCCTCC TGGGGCAGCT TTCTGGACAG GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC900CTCCTTGGAA CCCAGCTTCC TCCACAG927(2)SEQ ID NO:151的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:151:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240 CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CTTCCAACAC480CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CTGCGTCAGG540GAATTCGGCG GCAACGGCGG CAACATGGCG TCCCCAGCGC CGCCTGCTTG TGACCTCCGA600GTCCTCAGTA AACTGCTTCG TGACTCCCAT GTCCTTCACA GCAGACTGAG CCAGTGCCCA660GAGGTTCACC CTTTGCCTAC ACCTGTCCTG CTGCCTGCTG TGGACTTTAG CTTGGGAGAA720TGGAAAACCC AGATGGAGGA GACCAAGGCA CAGGACATTC TGGGAGCAGT GACCCTTCTG780CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA CTTGCCTCTC ATCCCTCCTG840GGGCAGCTTT CTGGACAGGT CCGTCTCCTC CTTGGGGCCC TGCAGAGCCT CCTTGGAACC900CAGCTTCCTC CACAGGGCAG GACCACA927(2)SEQ ID NO:152的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:152: GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA480GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC540GGCAACGGCG GCAACATGGC GTCCCCAGCG CCGCCTGCTT GTGACCTCCG AGTCCTCAGT600AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC660CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC720CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GCTGGAGGGA780GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GGGGCAGCTT840TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT900CCACAGGGCA GGACCACAGC TCACAAG927(2)SEQ ID NO:153的信息:
(i)序列特性:
(A)长度:927个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:153:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG480CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CGGCAACGGC540GGCAACATGG CGTCCCCAGC GCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT600CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT660ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG720GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA780GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG840GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC900AGGACCACAG CTCACAAGGA TCCCAAT927(2)SEQ ID NO:154的信息:
(i)序列特性:
(A)长度:906个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:154:GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT60TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT120CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT180ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT240CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC300TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC360CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT420CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA480GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC540GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT600CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT660ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG720GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA780 GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG840GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGGGCAG GACCACAGCT900CACAAG906(2)SEQ ID NO:155的信息:
(i)序列特性:
(A)长度:993个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:155:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GTCTTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC480GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG540 CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG600GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC660GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG720CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG780GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC840CTTGCGCAGC CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG900CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG CGATGGCGCA960GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA993(2)SEQ ID NO:156的信息:
(i)序列特性:
(A)长度:993个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:156:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240 TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GTCTCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG480GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT540GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA600GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA660CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA CACCATTAGG CCCTGCCAGC720TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT780GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG840GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG900GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG960CTCCTGCAGG CCCTGGAAGG GATATCCTAA TAA993(2)SEQ ID NO:157的信息:
(i)序列特性:
(A)长度:993个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:157: ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GTCTTCTGCT TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT480GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG540CCCGGCGGCG GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC600TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG660GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC720TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA780GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG840GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC900TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC960ACCCAGGGTG CCATGCCGGC CTTCGCCTAA TAA993(2)SEQ ID NO:158的信息:
(i)序列特性:
(A)长度:993个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:158:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GTCTATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG480CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG540CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CGGCGGCGGC600TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG660TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT720GCCACCTACA AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC780CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC840 CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AGGGATATCC900CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT TGCCACCACC960ATCTGGCAGC AGATGGAAGA ACTGGGATAA TAA993(2)SEQ ID NO:159的信息:
(i)序列特性:
(A)长度:993个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:159:ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GTCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC480CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG540TACCGCGTTC TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TACACCATTA600 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AGTGAGGAAG660ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC720CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC780TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC840CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG900GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA960CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA993(2)SEQ ID NO:160的信息:
(i)序列特性:
(A)长度:1027个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”
(xi)序列描述:SEQ ID NO:160:ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG300 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT540GACATGGCTA CACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT600TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC660ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC720TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA780CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC840GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC900TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA TCCTGGTTGC960TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC1020CTGATAA1027(2)SEQ ID NO:161的信息:
(i)序列特性:
(A)长度:155个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:161: Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu ThrLys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe145 150 155(2)SEQ ID NO:162的信息:
(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:162:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp ser His Val Leu His ser Arg Leu ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe ser Leu
35 40 45
Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60
Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
65 70 75 80
Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95
Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110
Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125
Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140
Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala
145 150 155 160
Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu
165 170 175
Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
180 185 190
His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
195 200 205
Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
210 215 220
Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
225 230 235 240
Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
245 250 255
Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Gly
260 265 270
Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gl
275 280 285
His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser
290 295 300
Thr Leu Cys Val Arg
305(2)SEQ ID NO:163的信息:
(i)序列特性:
(A)长度:312个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:163:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser145 150 155 160Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg
165 170 175Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His
180 185 190Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly
195 200 205Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly
210 215 220
Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu
225 230 235 240
Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val
245 250 255
Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro
260 265 270
Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu
275 280 285
Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val
290 295 300
Gly Gly Ser Thr Leu Cys Val Arg
305 310(2)SEQ ID NO:164的信息:
(i)序列特性:
(A)长度:313个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:164:
Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu
1 5 10 15
Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30
His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45
Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60
Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
65 70 75 80
Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95
Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110
Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125
Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140
Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala
145 150 155 160
Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu
165 170 175
Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
180 185 190
His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
195 200 205
Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
210 215 220
Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
225 230 235 240
Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
245 250 255
Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
260 265 270
Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
275 280 285
Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
290 295 300
Val Gly Gly Ser Thr Leu Cys Val Arg
305 310(2)SEQ ID NO:165的信息:
(i)序列特性:
(A)长度:316个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:165:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly145 150 155 160Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser
165 170 175Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys
180 185 190Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp
195 200 205Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln
210 215 220Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala225 230 235 240Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu
245 250 255Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly
260 265 270Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn
275 280 285
Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Pne
290 295 300
Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg
305 310 315(2)SEQ ID NO:166的信息:
(i)序列特性:
(A)长度:302个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:166:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125
Asn Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
130 135 140
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
145 150 155 160
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
165 170 175
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
180 185 190
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
195 200 205
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
210 215 220
Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
225 230 235 240
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val
245 250 255
Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly
260 265 270
Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile
275 280 285
Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
290 295 300(2)SEQ ID NO:167的信息:
(i)序列特性:
(A)长度:317个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:167:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
145 150 155 160
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala
165 170 175
Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu
180 185 190
Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
195 200 205
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr
210 215 220
Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
225 230 235 240
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala
245 250 255
Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser
260 265 270
Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly
275 280 285
Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln
290 295 300
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
305 310 315(2)SEQ ID NO:168的信息:
(i)序列特性:
(A)长度:302个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:168:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125Asn Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
130 135 140Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly145 150 155 160Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala
165 170 175Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu
180 185 190Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln
195 200 205Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu
210 215 220Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys225 230 235 240Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu
245 250 255Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
260 265 270
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
275 280 285
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
290 295 300(2)SEQ ID NO:169的信息:
(i)序列特性:
(A)长度:317个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:169:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 l0 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val
145 150 155 160
Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met
165 170 175
Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser
180 185 190
Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
195 200 205
Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
210 215 220
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
225 230 235 240
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
245 250 255
Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
260 265 270
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
275 280 285
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
290 295 300
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
305 310 315(2)SEQ ID NO:170的信息:
(i)序列特性:
(A)长度:302个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:170:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125
Asn Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro
130 135 140
Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
145 150 155 160
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His
165 170 175
Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu
180 185 190
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu
195 200 205
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu
210 215 220
Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
225 230 235 240
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
245 250 255
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
260 265 270
Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
275 280 285
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
290 295 300(2)SEQ ID NO:171的信息:
(i)序列特性:
(A)长度:317个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:171:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala145 150 155 160Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser
165 170 175His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu
180 185 190Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys
195 200 205Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln
210 215 220Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val225 230 235 240Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
245 250 255
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser
260 265 270
Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
275 280 285
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp
290 295 300
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
305 310 315(2)SEQ ID NO:172的信息:
(i)序列特性:
(A)长度:302个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:172:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125
Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
130 135 140
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu
145 150 155 160
Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly
165 170 175
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg
180 185 190
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
195 200 205
Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu
210 215 220
Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln
225 230 235 240
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln
245 250 255
Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
260 265 270
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
275 280 285
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
290 295 300(2)SEQ ID NO:173的信息:
(i)序列特性:
(A)长度:317个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:173:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg
145 150 155 160
Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
165 170 175
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser
180 185 190
Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys
195 200 205
Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr
210 215 220
Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly
225 230 235 240
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu
245 250 255
Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
260 265 270
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
275 280 285
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln
290 295 300
Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
305 310 315(2)SEQ ID NO:174的信息:
(i)序列特性:
(A)长度:302个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:174:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Prol 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125Asn Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
130 135 140Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His145 150 155 160Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu
165 170 175Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu
180 185 190Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu
195 200 205Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
210 215 220Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His225 230 235 240
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
245 250 255
Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
260 265 270
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala
275 280 285
Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala
290 295 300(2)SEQ ID NO:175的信息:
(i)序列特性:
(A)长度:317个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:175:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser
145 150 155 160
His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu
165 170 175
Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys
180 185 190
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln
195 200 205
Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val
210 215 220
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
225 230 235 240
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser
245 250 255
Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
260 265 270
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp
275 280 285
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro
290 295 300
Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala
305 310 315(2)SEQ ID NO:176的信息:
(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID N0:176:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125Asn Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
130 135 140His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln145 150 155 160Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
165 170 175Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
180 185 190Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
195 200 205Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
210 215 220Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg225 230 235 240Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val
245 250 255Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro
260 265 270Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
275 280 285Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala
290 295 300Thr305(2)SEQ ID NO:177的信息:
(i)序列特性:
(A)长度:320个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:177:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
145 150 155 160
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala
165 170 175
Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu
180 185 190
Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
195 200 205
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr
210 215 220
Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
225 230 235 240
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala
245 250 255
Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser
260 265 270
Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala
275 280 285
Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg
290 295 300
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
305 310 315 320(2)SEQ ID NO:178的信息:
(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:178:
Asn Cys SerIle Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125
Asn Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
130 135 140
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
145 150 155 160
Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala
165 170 175
Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu
180 185 190
Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln
195 200 205
Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu
210 215 220
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu
225 230 235 240
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu
245 250 255
Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
260 265 270
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
275 280 285
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
290 295 300
Ser
305(2)SEQ ID NO:179的信息:
(i)序列特性:
(A)长度:320个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:179:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val145 150 155 160Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met
165 170 175Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser
180 185 190Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
195 200 205Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
210 215 220Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys225 230 235 240Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln
245 250 255Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val
260 265 270
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
275 280 285
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser
290 295 300
Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile ser
305 310 315 320(2)SEQ ID NO:180的信息:
(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:180:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125
Asn Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro
130 135 140
Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
145 150 155 160
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg is
165 170 175
Leu Ala Gln Pro Thr Pro Lau Gly Pro Ala Ser Ser Leu Pro Gln Ser
180 185 190
Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly
195 200 205
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro
210 215 220
Glu Glu Leu Val Lau Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro
225 230 235 240
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser
245 250 255
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu
260 265 270
Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu
275 280 285
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
290 295 300
Gly
305(2)SEQ ID NO:181的信息:
(i)序列特性:
(A)长度:320个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:181:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
145 150 155 160
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser
165 170 175
His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu
180 185 190
Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe
195 200 205
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala
210 215 220
Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu
225 230 235 240
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu
245 250 255
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln
260 265 270
Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu
275 280 285
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
290 295 300
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
305 310 315 320(2)SEQ ID NO:182的信息:
(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:182:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
130 135 140Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu145 150 155 160Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu
165 170 175Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu
180 185 190Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
195 200 205Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
210 215 220His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln225 230 235 240
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
245 250 255
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
260 265 270
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
275 280 285
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
290 295 300
Pro
305(2)SEQ ID NO:183的信息:
(i)序列特性:
(A)长度:320个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:183:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg
145 150 155 160
Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
165 170 175
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly
180 185 190
Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln
195 200 205
Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
210 215 220
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
225 230 235 240
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala
245 250 255
Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu
260 265 270
Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
275 280 285
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr
290 295 300
Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
305 310 315 320(2)SEQ ID NO:184的信息:
(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:184:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser
115 120 125Asn Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
130 135 140Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His145 150 155 160Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser
165 170 175Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly
l80 185 190Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro
195 200 205Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro
210 215 220Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser225 230 235 240Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu
245 250 255Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu
260 265 270Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
275 280 285Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe
290 295 300Ala305(2)SEQ ID NO:185的信息:
(i)序列特性:
(A)长度:320个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:185:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro
1 5 10 15
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser
20 25 30
Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val
35 40 45
Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu
50 55 60
Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
65 70 75 80
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys
85 90 95
Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr
100 105 110
Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser
115 120 125
Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn
130 135 140
Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser
145 150 155 160
Mis Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu
165 170 175
Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe
180 185 190
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala
195 200 205
Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu
210 215 220
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu
225 230 235 240
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln
245 250 255
Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu
260 265 270
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
275 280 285
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
290 295 300
Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala
305 310 315 320(2)SEQ ID NO:186的信息:
(i)序列特性:
(A)长度:321个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:186:
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp
1 5 10 15
Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys
20 25 30
Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln
35 40 45
Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile
50 55 60
Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr
65 70 75 80
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn
85 90 95
Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro
100 105 110
Ala Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser
115 120 125
Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His
130 135 140
Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser
145 150 155 160
Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
165 170 175
Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
180 185 190
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
195 200 205
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
210 215 220
Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
225 230 235 240
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
245 250 255
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
260 265 270
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
275 280 285
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
290 295 300
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
305 310 315 320
Pro(2)SEQ ID NO:187的信息:
(i)序列特性:
(A)长度:321个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:187:Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu1 5 10 15Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala
20 25 30Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
35 40 45Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile
50 55 60Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu65 70 75 80Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp
85 90 95Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys
100 105 110Asn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser
115 120 125Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His
130 135 140Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser145 150 155 160Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
165 170 175Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
180 185 190Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
195 200 205Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
210 215 220Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly225 230 235 240His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
245 250 255Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
260 265 270
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
275 280 285
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
290 295 300
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
305 310 315 320
Pro(2)SEQ ID NO:188的信息:
(i)序列特性:
(A)长度:321个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:188:
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu
1 5 10 15
Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln
20 25 30
Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile
35 40 45
Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn
50 55 60
Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu
65 70 75 80
Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala
85 90 95
Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
100 105 110
Ala Thr Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser
115 120 125
Gly Pro Ile Ser ThrIle Asn Pro Ser Pro Pro Ser Lys Glu Ser His
130 135 140
Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser
145 150 155 160
Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
165 170 175
Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
180 185 190
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
195 200 205
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
210 215 220
Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
225 230 235 240
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
245 250 255
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
260 265 270
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
275 280 285
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
290 295 300
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
305 310 315 320
Pro(2)SEQ ID NO:189的信息:
(i)序列特性:
(A)长度:321个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:189:Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val1 5 10 15Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser
20 25 30Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro
35 40 45Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met
50 55 60Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val65 70 75 80Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu
85 90 95Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile
100 105 110Ile Ile Lys Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser
115 120 125Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His
130 135 140Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser145 150 155 160Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
165 170 175Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
180 185 190Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
195 200 205Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
210 215 220Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly225 230 235 240His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
245 250 255Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
260 265 270Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
275 280 285
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
290 295 300
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln
305 310 315 320
Pro(2)SEQ ID NO:190的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:190:
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp
1 5 10 15
Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys
20 25 30
Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln
35 40 45
Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile
50 55 60
Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr
65 70 75 80
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Gly
85 90 95
Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile
100 105 110
Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly Gly
115 120 125
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro
130 135 140
Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln
145 150 155 160
Gly Ala Me Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly
165 170 175
Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
180 185 190
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln
195 200 205
Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp
210 215 220
Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His
225 230 235 240
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala
245 250 255
Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu
260 265 270
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
275 280 285
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln
290 295 300
Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu
305 310 315 320
Leu Gly Met Ala Pro Ala Leu Gln Pro
325(2)SEQ ID NO:191的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:191:
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu
1 5 10 15
Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala
20 25 30Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
35 40 45Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Ser
50 55 50Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His65 70 75 80Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
85 90 95Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu
100 105 110Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly Gly
115 120 125Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Ash Pro
130 135 140Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln145 150 155 160Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly
165 170 175Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
180 185 190Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln
195 200 205Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp
210 215 220Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His225 230 235 240Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala
245 250 255Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu
260 265 270Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
275 280 285Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln
290 295 300Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu305 310 315 320Leu Gly Met Ala Pro Ala Leu Gln Pro
325(2)SEQ ID NO:192的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:192:
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu
1 5 10 15
Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln
20 25 30
Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn
35 40 45
Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro
50 55 60
Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile
65 70 75 80
Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg
85 90 95
Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg
100 105 110
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly Gly
115 120 125
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro
130 135 140
Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln
145 150 155 160
Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly
165 170 175
Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
180 185 190
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln
195 200 205
Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp
210 215 220
Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His
225 230 235 240
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala
245 250 255
Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu
260 265 270
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
275 280 285
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln
290 295 300
Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu
305 310 315 320
Leu Gly Met Ala Pro Ala Leu Gln Pro
325(2)SEQ ID NO:193的信息:
(i)序列特性:
(A)长度:299个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:193:
Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile
1 5 10 15
Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn
20 25 30
Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu
35 40 45
Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala
50 55 60
Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
65 70 75 80
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Tyr Val Glu
85 90 95
Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile
100 105 110
Asn Pro Ser Pro Pro Sar Lys Glu Ser His Lys Ser Pro Asn Met Ala
115 120 125
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala
130 135 140
Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser
145 150 155 160
Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly
165 170 175
Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln
180 185 190
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu
195 200 205
Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro
210 215 220
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly
225 230 235 240
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu
245 250 255
Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr
260 265 270
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met
275 280 285
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
290 295(2)SEQ ID NO:194的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:194:Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser
35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg
85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140Pro Asn Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu145 150 155 160Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
165 170 175Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
180 185 190Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu
195 200 205Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala
210 215 220Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu225 230 235 240Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg
245 250 255Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
260 265 270
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Gly Gly Gly Ser
275 280 285
Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe
290 295 300
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala
305 310 315 320
Ala Leu Gln Glu Lys Leu Cys Ala Thr
325(2)SEQ ID NO:195的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:195:
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
1 5 10 15
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
20 25 30
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser
35 40 45
Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60
Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro
65 70 75 80
Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg
85 90 95
Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
100 105 110
Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125
Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140
Pro Asn Met Ala Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu
145 150 155 160
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
165 170 175
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe
180 185 190
Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His
195 200 205
Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala
210 215 220
Gln Pro Gly Gly Gly Ser Asp Met Ala Thr Pro Leu Gly Pro Ala Ser
225 230 235 240
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys
245 250 255
Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr
260 265 270
Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly
275 280 285
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu
290 295 300
Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
305 310 315 320
Leu Leu Gln Ala Leu Glu Gly Ile Ser
325(2)SEQ ID NO:196的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:196:Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser
35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg
85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140Pro Asn Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val145 150 155 160Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
165 170 175His Leu Ala Gln Pro Gly Gly Gly Ser Asp Met Ala Thr Pro Leu Gly
180 185 190Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln
195 200 205Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
210 215 220Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His225 230 235 240Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala
245 250 255Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu
260 265 270Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
275 280 285
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr
290 295 300
Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
305 310 315 320
Thr Gln Gly Ala Met Pro Ala Phe Ala
325(2)SEQ ID NO:197的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:197:
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
1 5 10 15
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
20 25 30
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser
35 40 45
Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60
Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro
65 70 75 80
Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg
85 90 95
Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
100 105 110
Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125
Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140
Pro Asn Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met
145 150 155 160
Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val
155 170 175
Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
180 185 190
His Leu Ala Gln Pro Gly Gly Gly Ser Asp Met Ala Thr Pro Leu Gly
195 200 205
Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln
210 215 220
Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
225 230 235 240
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
245 250 255
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala
260 265 270
Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu
275 280 285
Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
290 295 300
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr
305 310 315 320
Ile Trp Gln Gln Met Glu Glu Leu Gly
325(2)SEQ ID NO:198的信息:
(i)序列特性:
(A)长度:329个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:198:Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser
35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg
85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe145 150 155 160Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
165 170 175Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Gly Gly
180 185 190Gly Ser Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln
195 200 205Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp
210 215 220Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His225 230 235 240Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala
245 250 255Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu
260 265 270Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
275 280 285
Leu Glu Gly Ile ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln
290 295 300
Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu
305 310 315 320
Leu Gly Met Ala Pro Ala Leu Gln Pro
325(2)SEQ ID NO:199的信息:
(i)序列特性:
(A)长度:319个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:199:
Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys
1 5 10 15
Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp
20 25 30
Gln Asp Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala
35 40 45
Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser
50 55 60
Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro
65 70 75 80
Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg
85 90 95
Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln
100 105 110
Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125
Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140
Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe
145 150 155 160
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
165 170 175
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly
180 185 190
Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
195 200 205
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala
210 215 220
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser
225 230 235 240
Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu
245 250 255
Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr
260 265 270
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro
275 280 285
Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
290 295 300
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
305 310 315(2)SEQ ID NO:200的信息:
(i)序列特性:
(A)长度:322个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:200:
Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys
1 5 10 15
Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp
20 25 30
Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala
35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser
50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile Ile Ile Arg Asp Gly Asp Trp Asn Glu Phe Arg
85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln
100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe145 150 155 160Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
165 170 175Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro
180 185 190Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu
195 200 205Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
210 215 220Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu225 230 235 240Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
245 250 255Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
260 265 270Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu
275 280 285Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala
290 295 300Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu305 310 315 320Gln Pro(2)SEQ ID NO:201的信息:
(i)序列特性:
(A)长度:319个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:201:
Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys
1 5 10 15
Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp
20 25 30
Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala
35 40 45
Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser
50 55 60
Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro
65 70 75 80
Thr Arg His Pro Ile Ile Ile Arg Asp Gly Asp Trp Asn Glu Phe Arg
85 90 95
Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln
100 105 110
Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125
Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140
Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe
145 150 155 160
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
165 170 175
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly
180 185 190
Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
195 200 205
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala
210 215 220
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser
225 230 235 240
Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu
245 250 255
Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr
260 265 270
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro
275 280 285
Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
290 295 300
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
305 310 315(2)SEQ ID NO:202的信息:
(i)序列特性:
(A)长度:322个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:202:
Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys
1 5 10 15
Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp
20 25 30
Gln Asp Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala
35 40 45
Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser
50 55 60
Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro
65 70 75 80
Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg
85 90 95
Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln
100 105 110
Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro
115 120 125
Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser
130 135 140
Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe
145 150 155 160
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
165 170 175
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro
180 185 190
Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu
195 200 205
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
210 215 220
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu
225 230 235 240
Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
245 250 255
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
260 265 270
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu
275 280 285
Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala
290 295 300
Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
305 310 315 320
Gln Pro(2)SEQ ID NO:203的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:203:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val145 150 155 160Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala
165 170 175Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala
180 185 190Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln
195 200 205Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu
210 215 220Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro225 230 235 240Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg
245 250 255Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly
260 265 270
Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu
275 280 285
Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln
290 295 300
Cys Pro
305(2)SEQ ID NO:204的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:204:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45
Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60
Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser
65 70 75 80
Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110
Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125
Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140
Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
145 150 155 160
Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
165 170 175
Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
180 185 190
Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
195 200 205
Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
210 215 220
Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
225 230 235 240
Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
245 250 255
Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala
260 265 270
Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu
275 280 285
Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
290 295 300
His Pro
305(2)SEQ ID NO:205的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:205:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys145 150 155 160Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr
165 170 175Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr
180 185 190Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu
195 200 205Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly
210 215 220Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln225 230 235 240His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser
245 250 255Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro
260 265 270Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His
275 280 285Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro
290 295 300Thr Pro305(2)SEQ ID NO:206的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:206:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45
Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60
Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser
65 70 75 80
Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110
Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125
Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140
Asn Met Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu
145 150 155 160
Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu
165 170 175
Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
180 185 190
Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu
195 200 205
Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala
210 215 220
His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg
225 230 235 240
Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
245 250 255
Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp
260 265 270
Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser
275 280 285
Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu
290 295 300
Leu Pro
305(2)SEQ ID NO:207的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:207:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45
Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60
Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser
65 70 75 80
Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110
Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125
Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140
Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr
145 150 155 160
Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val
165 170 175
Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu
180 185 190
Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser
195 200 205
Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys
210 215 220
Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys
225 230 235 240
Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
245 250 255
Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg
260 265 270
Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu
275 280 285
Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro
290 295 300
Ala Val
305(2)SEQ ID NO:208的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO :208:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp145 150 155 160Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg
165 170 175Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser
180 185 190Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr
195 200 205Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala
210 215 220Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu225 230 235 240Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn
245 250 255Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Lau Arg Val Leu Ser Lys
260 265 270
Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro
275 280 285
Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe
290 295 300
Ser Leu
305(2)SEQ ID NO:209的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:209:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45
Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60
Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser
65 70 75 80
Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110
Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125
Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140
Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly
145 150 155 160
Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln
165 170 175
Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile
180 185 190
Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met
195 200 205
Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met
210 215 220
Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu
225 230 235 240
Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu
245 250 255
Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser
260 265 270
Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile
275 280 285
Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly
290 295 300
Gln Leu
305(2)SEQ ID NO:210的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:210:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45
Val Arg Ala Val Lys Asn Leu Glu Asn Ala ser Gly Ile Glu Ala Ile
50 55 60
Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser
65 70 75 80
Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110
Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125
Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140
Asn Met Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys
145 150 155 160
Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys
165 170 175
Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
180 185 190
Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg
195 200 205
Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu
210 215 220
Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro
225 230 235 240
Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr
245 250 255
Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val
260 265 270
Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu
275 280 285
Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser
290 295 300
Leu Leu
305(2)SEQ ID NO:211的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:211:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu145 150 155 160Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val
165 170 175Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser
180 185 190Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg
195 200 205Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His
210 215 220
Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly
225 230 235 240
Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly
245 250 255
Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu
260 265 270
Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val
275 280 285
Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro
290 295 300
Pro Gln
305(2)SEQ ID NO:212的信息:
(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白
(xi)序列描述:SEQ ID NO:212:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
1 5 10 15
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45
Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60
Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser
65 70 75 80
Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His145 150 155 160Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr
165 170 175Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro
180 185 190Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val
195 200 205Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr
210 215 220Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr225 230 235 240Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu
245 250 255Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys
260 265 270Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu
275 280 285Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg
290 295 300Thr Thr305(2)SEQ ID NO:213的信息:(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:213:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg145 150 155 160Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
165 170 175Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp
180 185 190Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser
195 200 205Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu
210 215 220Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu225 230 235 240Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu
245 250 255Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
260 265 270Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu
275 280 285Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala
290 295 300His Lys305(2)SEQ ID NO:214的信息:(i)序列特性:
(A)长度:306个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:214:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val145 150 155 160Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe
165 170 175Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val
180 185 190Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser
195 200 205Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala
210 215 220Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys225 230 235 240Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met
245 250 255Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly
260 265 270Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu
275 280 285Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp
290 295 300Pro Asn305(2)SEQ ID NO:215的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:215:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val145 150 155 160Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala
165 170 175Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala
180 185 190Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln
195 200 205Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu
210 215 220Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro225 230 235 240Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg
245 250 255Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly
260 265 270Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser
275 280 285Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys
290 295 300Pro305(2)SEQ ID NO:216的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:216:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu145 150 155 160Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
165 170 175Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
180 185 190Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
195 200 205Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
210 215 220Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe225 230 235 240Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
245 250 255Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser
260 265 270Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg
275 280 285Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His
290 295 300Pro305(2)SEQ ID NO:217的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:217:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gin Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys145 150 155 160Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr
165 170 175Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr
180 185 190Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu
195 200 205Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly
210 215 220Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln225 230 235 240His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser
245 250 255Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pro Pro
260 265 270Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val
275 280 285Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr
290 295 300Pro305(2)SEQ ID NO:218的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:218:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp VaI
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu145 150 155 160Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu
165 170 175Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
180 185 190Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu
195 200 205Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala
210 215 220His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg225 230 235 240Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
245 250 255Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu
260 265 270Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg
275 280 285Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu
290 295 300Pro305(2)SEQ ID NO:219的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:219:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr145 150 155 160Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val
165 170 175Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu
180 185 190Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser
195 200 205Leu Leu Gly Thr GLn Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys
210 215 220Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys225 230 235 240Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
245 250 255Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val
260 265 270Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser
275 280 285Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala
290 295 300Val305(2)SEQ ID NO:220的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:220:Ala Asn Cys Ser Ile Meu Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp145 150 155 160Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg
165 170 175Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser
180 185 190Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr
195 200 205Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala
210 215 220Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu225 230 235 240Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met
245 250 255Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu
260 265 270Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu
275 280 285Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser
290 295 300Leu305(2)SEQ ID NO:221的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:221:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Iys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly145 150 155 160Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln
165 170 175Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile
180 185 190Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met
195 200 205Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala
210 215 220Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu225 230 235 240Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
245 250 255His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
260 265 270Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
275 280 285Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
290 295 300Leu305(2)SEQ ID NO:222的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:222:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys145 150 155 160Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys
165 170 175Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
180 185 190Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val
195 200 205Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser
210 215 220Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala225 230 235 240Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys
245 250 255Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met
260 265 270Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly
275 280 285Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu
290 295 300Leu305(2)SEQ ID NO:223的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:223:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu145 150 155 160Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val
165 170 175Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser Pro
180 185 190Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp
195 200 205Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro
210 215 220Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu225 230 235 240Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala
245 250 255Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly
260 265 270Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg
275 280 285Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro
290 295 300Gln305(2)SEQ ID NO:224的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:224:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu145 150 155 160Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val
165 170 175Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser Pro
180 185 190Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp
195 200 205Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro
210 215 220Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu225 230 235 240Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala
245 250 255Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly
260 265 270Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg
275 280 285Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro
290 295 300Gln305(2)SEQ ID NO:225的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:225:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 l0 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg145 150 155 160Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
165 170 175Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu
180 185 190Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg
195 200 205Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu
210 215 220Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu225 230 235 240Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly
245 250 255Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu
260 265 270Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln
275 280 285Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His
290 295 300Lys305(2)SEQ ID NO:226的信息:(i)序列特性:
(A)长度:305个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:226:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val145 150 155 160Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe
165 170 175Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu
180 185 190Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln
195 200 205Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Lau Leu Pro Ala Val
210 215 220Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala225 230 235 240Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala
245 250 255Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln
260 265 270Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu
275 280 285Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro
290 295 300Asn305(2)SEQ ID NO:227的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:227:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu145 150 155 160Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
165 170 175Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
180 185 190Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
195 200 205Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
210 215 220Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe225 230 235 240Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
245 250 255Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly
260 265 270Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser
275 280 285Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys
290 295 300Pro Glu Val His Pro305(2)SEQ ID NO:228的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:228:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu145 150 155 160Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
165 170 175Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
180 185 190Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
195 200 205Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
210 215 220Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe225 230 235 240Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
245 250 255Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly
260 265 270Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser
275 280 285Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys
290 295 300Pro Glu Val His Pro305(2)SEQ ID NO:229的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:229:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys145 150 155 160Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr
165 170 175Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr
180 185 190Cys Leu Set Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu
195 200 205Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly
210 215 220Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln225 230 235 240His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser
245 250 255Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser
260 265 270Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg
275 280 285Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His
290 295 300Pro Leu Pro Thr Pro305(2)SEQ ID NO:230的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:230:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu145 150 155 160Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu
165 170 175Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
180 185 190Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu
195 200 205Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala
210 215 220His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg225 230 235 240Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
245 250 255Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro
260 265 270Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val
275 280 285Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr
290 295 300Pro Val Leu Leu Pro305(2)SEQ ID NO:231的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:231:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IIe Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
l00 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr145 150 155 160Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val
165 170 175Met Ala Ala Arg Gly Gln Lau Gly Pro Thr Cys Leu Ser Ser Leu Leu
180 185 190Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser
195 200 205Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys
210 215 220Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys225 230 235 240Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
245 250 255Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys
260 265 270Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His
275 280 285Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val
290 295 300Leu Leu Pro Ala Val305(2)SEQ ID NO:232的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:232:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp145 150 155 160Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg
165 170 175Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser
180 185 190Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr
195 200 205Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala
210 215 220Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu225 230 235 240Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn
245 250 255Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val
260 265 270Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser
275 280 285Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala
290 295 300Val Asp Phe Ser Leu305(2)SEQ ID NO:233的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:233:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly145 150 155 160Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln
165 170 175Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile
180 185 190Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met
195 200 205Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly
210 215 220Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu225 230 235 240Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln
245 250 255Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val
260 265 270Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala
275 280 285Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala
290 295 300Ala Arg Gly Gln Leu305(2)SEQ ID NO:234的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:234:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys145 150 155 160Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys
165 170 175Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
180 185 190Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys
195 200 205Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His
210 215 220Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val225 230 235 240Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met
245 250 255Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu
260 265 270Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser
275 280 285Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala
290 295 300Leu Gln Ser Leu Leu305(2)SEQ ID NO:235的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:235:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Argl 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu145 150 155 160Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val
165 170 175Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly Asn
180 185 190Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys
195 200 205Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro
210 215 220Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe225 230 235 240Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp
245 250 255Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg
260 265 270Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser
275 280 285Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr
290 295 300Gln Leu Pro Pro Gln305(2)SEQ ID NO:236的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:236:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His145 150 155 160Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr
165 170 175Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro
180 185 190Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp
195 200 205Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro
210 215 220Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu225 230 235 240Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala
245 250 255Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly
260 265 270Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg
275 280 285Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro
290 295 300Gln Gly Arg Thr Thr305(2)SEQ ID NO:237的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:237:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg145 150 155 160Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
165 170 175Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro
180 185 190Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val
195 200 205Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr
210 215 220Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr225 230 235 240Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu
245 250 255Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys
260 265 270Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu
275 280 285Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg
290 295 300Thr Thr Ala His Lys305(2)SEQ ID NO:238的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:238:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val145 150 155 160Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe
165 170 175Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp
180 185 190Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser
195 200 205Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu
210 215 220Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu225 230 235 240Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu
245 250 255Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
260 265 270Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu
275 280 285Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala
290 295 300His Lys Asp Pro Asn305(2)SEQ ID NO:239的信息:(i)序列特性:
(A)长度:302个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:239:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg145 150 155 160Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val
165 170 175Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp
180 185 190Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser
195 200 205Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu
210 215 220Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu225 230 235 240Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu
245 250 255Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
260 265 270Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu
275 280 285Gln Ser Leu Leu Gly Thr Gln Gly Arg Thr Thr Ala His Lys
290 295 300(2)SEQ ID NO:240的信息:(i)序列特性:
(A)长度:83个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:240:AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT60ACGTAGAGGG CGGTGGAGGC TCC83(2)SEQ ID NO:241的信息:(i)序列特性:
(A)长度:82个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:241:CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AAGTTTTCAG60ATAGAAGGTC AGTTTACGAC GG82(2)SEQ ID NO:242的信息:(i)序列特性:
(A)长度:8个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:242:Gly Gly Gly Ser Gly Gly Gly Ser1 5(2)SEQ ID NO:243的信息:(i)序列特性:
(A)长度:12个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:243:Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser1 5 10(2)SEQ ID NO:244的信息:(i)序列特性:
(A)长度:7个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:244:Ser Gly Gly Ser Gly Gly Ser1 5(2)SEQ ID NO:245的信息:(i)序列特性:
(A)长度:6个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:245:Glu Phe Gly Asn Met Ala1 5(2)SEQ ID NO:246的信息:(i)序列特性:
(A)长度:7个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:246:Glu Phe Gly Gly Asn Asn Ala1 5(2)SEQ ID NO:247的信息:(i)序列特性:
(A)长度:10个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:247:Glu Phe Gly Gly Asn Gly Gly Asn Met Ala1 5 10(2)SEQ ID NO:248的信息:(i)序列特性:
(A)长度:309个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:248:Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg1 5 10 15Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val
20 25 30Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe
35 40 45Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile
50 55 60Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser65 70 75 80Arg His Pro Ile Ile Leu Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
85 90 95Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln
100 105 110Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile
115 120 125Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro
130 135 140Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu145 150 155 160Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Asn Asp Ile Leu
165 170 175Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
180 185 190Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
195 200 205Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
210 215 220Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe225 230 235 240Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
245 250 255Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly
260 265 270Asn Met Ala Ser Pro Ala Pro Pro Ala Ser Asp Leu Arg Val Leu Ser
275 280 285Lys Leu Leu Lys Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys
290 295 300Pro Glu Val His Pro305(2)SEQ ID NO:249的信息:(i)序列特性:
(A)长度:459个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:249:TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGG459(2)SEQ ID NO:250的信息:(i)序列特性:
(A)长度:447个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:250:TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGGGCAGGA CCACAGCTCA CAAGGATCCC360AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT420GTAGGAGGGT CCACCCTCTG CGTCAGG447(2)SEQ ID NO:251的信息:(i)序列特性:
(A)长度:459个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:251:TCCCCAGCGC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT60GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG120CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA180CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA240CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC300CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT360CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT420TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGG459(2)SEQ ID NO:252的信息:(i)序列特性:
(A)长度:153个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:252:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg145 150(2)SEQ ID NO:253的信息:(i)序列特性:
(A)长度:149个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:253:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Gly
100 105 110Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln
115 120 125His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser
130 135 140Thr Leu Cys Val Arg145(2)SEQ ID NO:254的信息:(i)序列特性:
(A)长度:153个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:蛋白(xi)序列描述:SEQ ID NO:254:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu
100 105 110Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg145 150(2)SEQ ID NO:255的信息:(i)序列特性:
(A)长度:64个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:255:GGATCCACCA TGAGCCGCCT GCCCGTCCTG CTCCTGCTCC AACTCCTGGT CCGCCCCGCC60ATGG64(2)SEQ ID NO:256的信息:(i)序列特性:
(A)长度:153个氨基酸
(B)类型:氨基酸
(C)链型:未知
(D)拓扑结构:未知(ii)分子类型:蛋白(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:112
(D)其他信息:/注释=“在第112位缺失或是Leu、Ala、
Val、Ile、Pro、Phe、Trp或Met”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:113
(D)其他信息:/注释=“在第113位缺失或是Pro、Phe、
Ala、Val、Leu、Ile、Trp或Met”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:114
(D)其他信息:/注释=“在第114位缺失或是Pro、Phe、
Ala、Val、Leu、Ile、Trp或Met”(ix)特征:
(A)名称/关键词:修饰位点
(B)位置:115
(D)其他信息:/注释=“在第115位缺失或是Gln、Gly、
Ser、Thr、Tyr或Asn”(xi)序列描述:SEQ ID NO:256:Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu1 5 10 15Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val
20 25 30His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu
35 40 45Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu
50 55 60Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln65 70 75 80Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln
85 90 95Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Xaa
100 105 110Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
115 120 125Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu
130 135 140Val Gly Gly Ser Thr Leu Cys Val Arg145 150(2)SEQ ID NO:257的信息:(i)序列特性:
(A)长度:464个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:257:CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG60CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGATCGAA120ACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT180CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC240CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA300CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAGAG GGCGGTGGAG360GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT CCGTCTAAAG420AATCTCATAA ATCTCCAAAC ATGTAAGGTA CCGCATGCAA GCTT464(2)SEQ ID NO:258的信息:(i)序列特性:
(A)长度:419个碱基对
(B)类型:核苷酸
(C)链型:单链
(D)拓扑结构:线性(ii)分子类型:其他核苷酸
(A)描述:/desc=“DNA(合成物)”(xi)序列描述:SEQ ID NO:258:CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG60CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGATCGAA120ACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT180CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC240CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA300CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAGAG GGCGGTGGAG360GCTCCCCGGG TGGTGGTTCT GGCGGCGGCT CCAACATGTA AGGTACCGCA TGCAAGCTT419
Claims (33)
1.一种造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1和R2分别独立地选自下组:
(I)一种多肽,包括:有下述通式的修饰的人G-CSF的氨基酸序列:1 10Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
20Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
30 40Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
50Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
60 70Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
120 130Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
150 160Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro(SEQ ID NO:1)其中Xaa在位点1是Thr,Ser,Arg,Tyr或Gly;Xaa在位点2是Pro或Leu;Xaa在位点3是Leu,Arg,Tyr或Ser;Xaa在位点13是Phe,Ser,His,Thr或Pro;Xaa在位点16是Lys,Pro,Ser,Thr或His;Xaa在位点17是Cys,Ses,Gly,Ala,Ile,Tyr或Arg;Xaa在位点18是Leu,Thr,Pro,His,Ile或Cys;Xaa在位点22是Arg,Tyr,Ser,Thr或Ala;Xaa在位点24是Ile,Pro,Tyr或Leu;Xaa在位点27是Asp或Gly;Xaa在位点30是Ala,Ile,Leu或Gly;Xaa在位点34是Kys或Ser;Xaa在位点36是Cys或Ser;Xaa在位点42是Cys或Ser;Xaa在位点43是His,Thr,Gly,Val,Lys,Trp,Ala,Arg,Cys或Leu;Xaa在位点44是Pro,Gly,Arg,Asp,Val,Ala,His,Trp,Gln或Thr;Xaa在位点46是Glu,Arg,Phe,Arg,Ile或Ala;Xaa在位点47是Leu或Thr;Xaa在位点49是Leu,Phe,Arg或Ser;Xaa在位点50是Leu,Ile,His,Pro或Tyr;Xaa在位点54是Leu或His;Xaa在位点64是Cys或Ser;Xaa在位点67是Gln,Lys,Leu或Cys;Xaa在位点70是Gln,Pro,Leu,Arg或Ser;Xaa在位点74是Cys或Ser;Xaa在位点104是Asp,Gly或Val;Xaa在位点108是Leu,Lea,Val,Arg,Trp,Gln或Gly;Xaa在位点115是Thr,His,Leu或Ala;Xaa在位点120是Gln,Gly,Arg,Lys或His;Xaa在位点123是Glu,Arg,Phe或Thr;Xaa在位点144是Phe,His,Arg,Pro,Leu,Gln或Glu;Xaa在位点146是Arg或Gln;Xaa在位点147是Arg或Gln;Xaa在位点156是His,Gly或Ser;Xaa在位点159是Ser,Arg,Thr,Tyr,Val或Gly;Xaa在位点162是Glu,Leu,Gly或Trp;Xaa在位点163是Val,Gly,Arg或Ala;Xaa在位点169是Arg,Ser,Leu,Arg或Cys;Xaa在位点170是His,Arg或Ser;
其中任选地可从所说的修饰的人G-CSF氨基酸序列删除N-末端的1-11氨基酸和C-末端的1-5氨基酸;并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-137
57-58 95-96 137-138
58-59 96-97 138-139
59-60 97-98 139-140
60-61 98-99 140-141
61-62 99-100 141-142
或142-143
(II)一种多肽,包括:有下述通式的修饰的人IL-3的氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130(SEQ ID NO:2)其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln, Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Aly,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Vaa,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala,或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Glu,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser, Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr, Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr,或Leu;Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中任选地可从所说修饰的人IL-3氨基酸序列删除N-末端的1-14氨基酸和C-末端的1-15氨基酸;其中被称为Xaa的1-44氨基酸与1-133位天然人白介素-3对应的氨基酸不同;
并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N和C-末端;
26-27 49-50 83-84
27-28 50-51 84-85
28-29 51-52 85-86
29-30 52-53 86-87
30-31 53-54 87-88
31-32 54-55 88-89
32-33 64-65 89-90
33-34 65-66 90-91
34-35 66-67 91-92
35-36 67-68 92-93
36-37 68-69 97-98
37-38 69-70 98-99
38-39 70-71 99-100
39-40 71-72 100-101
40-41 72-73 101-102
41-42 82-83 102-103
or 103-104
(III)一种多肽,包括有下述通式的修饰的人c-mpl配体的氨基酸序列:SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer1 5 10 15HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro20 25 30 35ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu40 45 50 55ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis115 120 125 130LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal135 140 145 150Arg(SEQ ID NO:256)153其中;Xaa在位点112被删去或者是Leu,Ala,Val,Ile,Pro,Phe,Trp,或Met;Xaa在位点113被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点114被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点115被删去或者是Gln,Gly,Ser,Thr,Tyr,或Asn;和
并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N和C-末端;
26-27 51-52 108-109
27-28 52-53 109-110
28-29 53-54 110-111
29-30 54-55 111-112
30-31 55-56 112-113
32-33 56-57 113-114
33-34 57-58 114-115
34-35 58-59 115-116
36-37 59-60 116-117
37-38 78-79 117-118
38-39 79-80 118-119
40-41 80-81 119-120
41-42 81-82 120-121
42-43 82-83 121-122
43-44 83-84 122-123
44-45 84-85 123-124
46-47 85-86 124-125
47-48 86-87 125-126
48-49 87-88 126-127
50-51 88-89 or 127-128
(IV)一种集落刺激因子;并且其中L1是能够将R1连接到R2上的接头;前提是至少R1或R2是选自通式(I),(II),(III)的多肽;以及所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
2.权利要求1的造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1和R2分别独立地选自下组:
(I)一种多肽,包括:有下述通式的修饰的人G-CSF的氨基酸序列:1 10Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
20Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
30 40Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
50Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
60 70Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
120 130Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
150 160Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro(SEQ ID NO:1)其中Xaa在位点1是Thr,Ser,Arg,Tyr或Gly;Xaa在位点2是Pro或Leu;Xaa在位点3是Leu,Arg,Tyr或Ser;Xaa在位点13是Phe,Ser,His,Thr或Pro;Xaa在位点16是Lys,Pro,Ser,Thr或His;Xaa在位点17是Cys,Ser,Gly,Ala,Ile,Tyr或Arg;Xaa在位点18是Leu,Thr,Pro,His,Ile或Cys;Xaa在位点22是Arg,Tyr,Ser,Thr或Ala;Xaa在位点24是Ile,Pro,Tyr或Leu;Xaa在位点27是Asp或Gly;Xaa在位点30是Ala,Ile,Leu或Gly;Xaa在位点34是Lys或Ser;Xaa在位点36是Cys或Ser;Xaa在位点42是Cys或Ser;Xaa在位点43是His,Thr,Gly,Val,Lys,Trp,Ala,Arg,Cys或Leu;Xaa在位点44是Pro,Gly,Arg,Asp,Val,Ala,His,Trp,Gln或Thr;Xaa在位点46是Glu,Arg,Phe,Arg,Ile或Ala;Xaa在位点47是Leu或Thr;Xaa在位点49是Leu,Phe,Arg或Ser;Xaa在位点50是Leu,Ile,His,Pro或Tyr;Xaa在位点54是Leu或His;Xaa在位点64是Cys或Ser;Xaa在位点67是Gln,Lys,Leu或Cys;Xaa在位点70是Gln,Pro,Leu,Arg或Ser;Xaa在位点74是Cys或Ser;Xaa在位点104是Asp,Gly或Val;Xaa在位点108是Leu,Ala,Val,Arg,Trp,Gln或Gly;Xaa在位点115是Thr,His,Leu或Ala;Xaa在位点120是Gln,Gly,Arg,Lys或His;Xaa在位点123是Glu,Arg,Phe或Thr;Xaa在位点144是Phe,His,Arg,Pro,Leu,Gln或Glu;Xaa在位点146是Arg或Gln;Xaa在位点147是Arg或Gln;Xaa在位点156是His,Gly或Ser;Xaa在位点159是Ser,Arg,Thr,Tyr,Val或Gly;Xaa在位点162是Glu,Leu,Gly或Trp;Xaa在位点163是Val,Gly,Arg或Ala;Xaa在位点169是Arg,Ser,Leu,Arg或Cys;Xaa在位点170是His,Arg或Ser;
其中任选地可从所说修饰的人G-CSF氨基酸序列删除N-末端的1-11氨基酸和C-末端的1-5氨基酸;并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-137
57-58 95-96 137-138
58-59 96-97 138-139
59-60 97-98 139-140
60-61 98-99 140-141
61-62 99-100 141-142
or 142-143
(II)一种多肽,包括:有下述通式的修饰的人hIL-3的氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Ala,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala,或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser,Lys,Gln,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Sep,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点7l是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Gly,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr,或Leu;Xaa在位点78是Leu,ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn、His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Gly,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中任选地可从所说修饰的人IL-3氨基酸序列删除N-末端的1-14氨基酸和/或C-末端的1-15氨基酸;其中被称为Xaa的1-44氨基酸与1-133位天然人白介素-3对应的氨基酸不同;
并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N和C-末端;
26-27 49-50 83-84
27-28 50-51 84-85
28-29 51-52 85-86
29-30 52-53 86-87
30-31 53-54 87-88
31-32 54-55 88-89
32-33 64-65 89-90
33-34 65-66 90-91
34-35 66-67 91-92
35-36 67-68 92-93
36-37 68-69 97-98
37-38 69-70 98-99
38-39 70-71 99-100
39-40 71-72 100-101
40-41 72-73 101-102
41-42 82-83 102-103
或103-104
(III)一种多肽,包括有下述通式的修饰的人c-mpl配体的氨基酸序列:SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer1 5 10 15HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro20 25 30 35ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu40 45 50 55ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis115 120 125 130LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal135 140 145 150Arg(SEQ ID N0:256)153其中;Xaa在位点112被删去或者是Leu,Ala,Val,Ile,Pro,Phe,Trp,或Met;Xaa在位点113被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点114被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点115被删去或者是Gln,Gly,Ser,Thr,Tyr,或Asn;和
并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N和C-末端;
52-53 108-109
53-54 109-110
54-55 110-111
55-56 111-112
56-57 112-113
57-58 113-114
58-59 114-115
59-60 115-116
78-79 116-117
79-80 117-118
80-81 118-119
81-82 119-120
82-83 120-121
83-84 121-122
84-85 122-123
85-86 123-124
86-87 124-125
87-88 125-126
88-89 126-127
or 127-128以及
(IV)一种集落刺激因子;并且其中L1是能够将R1连接到R2上的接头;前提是至少R1或R2是选自通式(I),(II),(III)的多肽;以及所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
3.权利要求1的造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1是一种多肽,包括具有如下通式的修饰人G-CSF的氨基酸序列:1 10Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
20Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
30 40Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
50Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
60 70Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
120 130Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
150 160Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro(SEQ ID NO:1)其中Xaa在位点1是Thr,Ser,Arg,Tyr或Gly;Xaa在位点2是Pro或Leu;Xaa在位点3是Leu,Arg,Tyr或Ser;Xaa在位点13是Phe,Ser,His,Thr或Pro;Xaa在位点16是Lys,Pro,Ser,Thr或His;Xaa在位点17是Cys,Ser,Gly,Ala,Ile,Tyr或Arg;Xaa在位点18是Leu,Thr,Pro,His,Ile或Cys;Xaa在位点22是Arg,Tyr,Ser,Thr或Ala;Xaa在位点24是Ile,Pro,Tyr或Leu;Xaa在位点27是Asp或Gly;Xaa在位点30是Ala,Ile,Leu或Gly;Xaa在位点34是Lys或Ser;Xaa在位点36是Cys或Ser;Xaa在位点42是Cys或Ser;Xaa在位点43是His,Thr,Gly,Val,Lys,Trp,Ala,Arg,Cys或Leu;Xaa在位点44是Pro,Gly,Arg,Asp,Val,Ala,His,Trp,Gln或Thr;Xaa在位点46是Glu,Arg,Phe,Arg,Ile或Ala;Xaa在位点47是Leu或Thr;Xaa在位点49是Leu,Phe,Arg或Ser;Xaa在位点50是Leu,Ile,His,Pro或Tyr;Xaa在位点54是Leu或His;Xaa在位点64是Cys或Ser;Xaa在位点67是Gln,Lys,Leu或Cys;Xaa在位点70是Gln,Pro,Leu,Arg或Ser;Xaa在位点74是Cys或Ser;Xaa在位点104是Asp,Gly或Val;Xaa在位点108是Leu,Ala,Val,Arg,Trp,Gln或Gly;Xaa在位点115是Thr,His,Leu或Ala;Xaa在位点120是Gln,Gly,Arg,Lys或His;Xaa在位点123是Glu,Arg,Phe或Thr;Xaa在位点144是Phe,His,Arg,Pro,Leu,Gln或Glu;Xaa在位点146是Arg或Gln;Xaa在位点147是Arg或Gln;Xaa在位点156是His,Gly或Ser;Xaa在位点159是Ser,Arg,Thr,Tyr,Val或Gly;Xaa在位点162是Glu,Leu,Gly或Trp;Xaa在位点163是Val,Gly,Arg或Ala;Xaa在位点169是Arg,Ser,Leu,Arg或Cys;Xaa在位点170是His,Arg或Ser;
其中任选地可从所说修饰的人G-CSF氨基酸序列删除N-末端的1-11氨基酸和C-末端的1-5氨基酸;并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-137
57-58 95-96 137-138
58-59 96-97 138-139
59-60 97-98 139-140
60-61 98-99 140-141
61-62 99-100 141-142
或142-143
其中R2是一种多肽,包括有如下通式的修饰的人IL-3的氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130(SEQ ID NO:2)其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Tlu,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Ala,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala,或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr,或Leu;Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln、Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中任选地可从所说修饰的人IL-3氨基酸序列删除N-末端的1-14氨基酸和/或C-末端的1-15氨基酸;其中被称为Xaa的1-44氨基酸与1-133位天然人白介素-3对应的氨基酸不同;
并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N和C-末端;
26-27 49-50 83-84
27-28 50-51 84-85
28-29 51-52 85-86
29-30 52-53 86-87
30-31 53-54 87-88
31-32 54-55 88-89
32-33 64-65 89-90
33-34 65-66 90-91
34-35 66-67 91-92
35-36 67-68 92-93
36-37 68-69 97-98
37-38 69-70 98-99
38-39 70-71 99-100
39-40 71-72 100-101
40-41 72-73 101-102
41-42 82-83 102-103
or 103-104
其中L1是能够将R1连接到R2上的接头;并且所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
4.权利要求1的造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1是一种多肽,包括具有如下通式的修饰人G-CSF的氨基酸序列:1 10Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
20Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
30 40Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
50Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
60 70Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
120 130Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
150 160Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro(SEQ ID NO:1)其中Xaa在位点1是Thr,Ser,Arg,Tyr或Gly;Xaa在位点2是Pro或Leu;Xaa在位点3是Leu,Arg,Tyr或Ser;Xaa在位点13是Phe,Ser,His,Thr或Pro;Xaa在位点16是Lys,Pro,Ser,Thr或His;Xaa在位点17是Cys,Ser,Gly,Ala,Ile,Tyr或Arg;Xaa在位点18是Leu,Thr,Pro,His,Ile或Cys;Xaa在位点22是Arg,Tyr,Ser,Thr或Ala;Xaa在位点24是Ile,Pro,Tyr或Leu;Xaa在位点27是Asp或Gly;Xaa在位点30是Ala,Ile,Leu或Gly;Xaa在位点34是Lys或Ser;Xaa在位点36是Cys或Ser;Xaa在位点42是Cys或Ser;Xaa在位点43是His,Thr,Gly,Val,Lys,Trp,Ala,Arg,Cys或Leu;Xaa在位点44是Pro,Gly,Arg,Asp,Val,Ala,His,Trp,Gln或Thr;Xaa在位点46是Glu,Arg,Phe,Arg,Ile或Ala;Xaa在位点47是Leu或Thr;Xaa在位点49是Leu,Phe,Arg或Ser;Xaa在位点50是Leu,Ile,His,Pro或Tyr;Xaa在位点54是Leu或His;Xaa在位点64是Cys或Ser;Xaa在位点67是Gln,Lys,Leu或Cys;Xaa在位点70是Gln,Pro,Leu,Arg或Ser;Xaa在位点74是Cys或Ser;Xaa在位点104是Asp,Gly或Val;Xaa在位点108是Leu,Ala,Val,Arg,Trp,Gln或Gly;Xaa在位点115是Thr,His,Leu或Ala;Xaa在位点120是Gln,Gly,Arg,Lys或His;Xaa在位点123是Glu,Arg,Phe或Thr;Xaa在位点144是Phe,His,Arg,Pro,Leu,Gln或Glu;Xaa在位点146是Arg或Gln;Xaa在位点147是Arg或Gln;Xaa在位点156是His,Gly或Ser;Xaa在位点159是Ser,Arg,Thr,Tyr,Val或Gly;Xaa在位点162是Glu,Leu,Gly或Trp;Xaa在位点163是Val,Gly,Arg或Ala;Xaa在位点169是Arg,Ser,Leu,Arg或Cys;Xaa在位点170是His,Arg或Ser;
其中任选地可从所说修饰的人G-CSF氨基酸序列删除N-末端的1-11氨基酸和C-末端的1-5氨基酸;并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-137
57-58 95-96 137-138
58-59 96-97 138-139
59-60 97-98 139-140
60-61 98-99 140-141
61-62 99-100 141-142
或142-143R2是一种多肽,包括有如下通式的修饰的人IL-3的氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Ala,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala,或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr或Leu;Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中任选地可从所说修饰的人IL-3氨基酸序列删除N-末端的1-14氨基酸和/或C-末端的1-15氨基酸;其中被称为Xaa的1-44氨基酸与1-133位天然人白介素-3对应的氨基酸不同;
其中L1是能够将R1连接到R2上的接头;并且所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
5.权利要求1的造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1是一种多肽,包括具有如下通式的修饰人G-CSF的氨基酸序列:1 10Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa
20Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly
30 40Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa
50Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp
60 70Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly
80Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
90 100Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
110Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp
120 130Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr
140Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala
150 160Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa
170Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro(SEQ ID NO:1)其中Xaa在位点1是Thr,Se,Arg,Tyr或Gly;Xaa在位点2是Pro或Leu;Xaa在位点3是Leu,Arg,Tyr或Ser;Xaa在位点13是Phe,Ser,His,Thr或Pro;Xaa在位点16是Lys,Pro,Ser,Thr或His;Xaa在位点17是Cys,Ser,Gly,Ala,Ile,Tyr或Arg;Xaa在位点18是Leu,Thr,Pro,His,Ile或Cys;Xaa在位点22是Arg,Tyr,Ser,Thr或Ala;Xaa在位点24是Ile,Pro,Tyr或Leu;Xaa在位点27是Asp或Gly;Xaa在位点30是Ala,Ile,Leu或Gly;Xaa在位点34是Lys或Ser;Xaa在位点36是Cys或Ser;Xaa在位点42是Cys或Ser;Xaa在位点43是His,Thr,Gly,Val,Lys,Trp,Ala,Arg,Cys或Leu;Xaa在位点44是Pro,Gly,Arg,Asp,Val,Ala,His,Trp,Gln或Thr;Xaa在位点46是Glu,Arg,Phe,Arg,Ile或Ala;Xaa在位点47是Leu或Thr;Xaa在位点49是Leu,Phe,Arg或Ser;Xaa在位点50是Leu,Ile,His,Pro或Tyr;Xaa在位点54是Leu或His;Xaa在位点64是Cys或Ser;Xaa在位点67是Gln,Lys,Leu或Cys;Xaa在位点70是Gln,Pro,Leu,Arg或Ser;Xaa在位点74是Cys或Ser;Xaa在位点104是Asp,Gly或Val;Xaa在位点108是Leu,Ala,Val,Arg,Trp,Gln或Gly;Xaa在位点115是Thr,His,Leu或Ala;Xaa在位点120是Gln,Gly,Arg,Lys或His;Xaa在位点123是Glu,Arg,Phe或Thr;Xaa在位点144是Phe,His,Arg,Pro,Leu,Gln或Glu;Xaa在位点146是Arg或Gln;Xaa在位点147是Arg或Gln;Xaa在位点156是His,Gly或Ser;Xaa在位点159是Ser,Arg,Thr,Tyr,Val或Gly;Xaa在位点162是Glu,Leu,Gly或Trp;Xaa在位点163是Val,Gly,Arg或Ala;Xaa在位点169是Arg,Ser,Leu,Arg或Cys;Xaa在位点170是His,Arg或Ser;
其中任选地可从所说修饰的人G-CSF氨基酸序列删除N-末端的1-11氨基酸和C-末端的1-5氨基酸;并且其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
38-39 62-63 123-124
39-40 63-64 124-125
40-41 64-65 125-126
41-42 65-66 126-127
42-43 66-67 128-129
43-44 67-68 128-129
45-46 68-69 129-130
48-49 69-70 130-131
49-50 70-71 131-132
52-53 71-72 132-133
53-54 91-92 133-134
54-55 92-93 134-135
55-56 93-94 135-136
56-57 94-95 136-137
57-58 95-96 137-138
58-59 96-97 138-139
59-60 97-98 139-140
60-61 98-99 140-141
61-62 99-100 141-142
或142-143R2是一种多肽,包括有如下通式的修饰的人c-mpl的氨基酸序列:SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer1 5 10 15HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro20 25 30 35ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu40 45 50 55ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis115 120 125 130LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal135 140 145 150Arg(SEQ ID NO:256)153其中;Xaa在位点112被删去或者是Leu,Ala,Val,Ile,Pro,Phe,Trp,或Met;Xaa在位点113被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点114被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点115被删去或者是Gln,Gly,Ser,Thr,Tyr,或Asn;和
其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
26-27 51-52 108-109
27-28 52-53 109-110
28-29 53-54 110-111
29-30 54-55 111-112
30-31 55-56 112-113
32-33 56-57 113-114
33-34 57-58 114-115
34-35 58-59 115-116
36-37 59-60 116-117
37-38 78-79 117-118
38-39 79-80 118-119
40-41 80-81 119-120
41-42 81-82 120-121
42-43 82-83 121-122
43-44 83-84 122-123
44-45 84-85 123-124
46-47 85-86 124-125
47-48 86-87 125-126
48-49 87-88 126-127
50-51 88-89 or 127-128;
其中L1是能够将R1连接到R2上的接头;并且所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
6.权利要求1的造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1是一种多肽,包括具有如下通式的修饰人c-mpl的氨基酸序列:SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer1 5 10 15HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro20 25 30 35ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu40 45 50 55ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis115 120 125 130LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal135 140 145 150Arg(SEQ ID NO:256)153其中;Xaa在位点112被删去或者是Leu,Ala,Val,Ile,Pro,Phe,Trp,或Met;Xaa在位点113被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点114被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点115被删去或者是Gln,Gly,Ser,Thr,Tyr,或Asn;和
其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
26-27 51-52 108-109
27-28 52-53 109-110
28-29 53-54 110-111
29-30 54-55 111-112
30-31 55-56 112-113
32-33 56-57 113-114
33-34 57-58 114-115
34-35 58-59 115-116
36-37 59-60 116-117
37-38 78-79 117-118
38-39 79-80 118-119
40-41 80-81 119-120
41-42 81-82 120-121
42-43 82-83 121-122
43-44 83-84 122-123
44-45 84-85 123-124
46-47 85-86 124-125
47-48 86-87 125-126
48-49 87-88 126-127
50-51 88-89 or 127-128;
其中R2是一种多肽,包括有如下通式的修饰的人IL-3的氨基酸序列:Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe
125 130其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln,或Arg;Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg,或Gln;Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala,或Cys;Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro,或Ala;Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser,或
Val;Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或
Gly;Xaa在位点23是Ile,Val,Ala,Gly,Trp,Lys,Phe,Leu,Ser,或Arg;Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe,或Leu;Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro,或Ala;Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala或Trp;Xaa在位点27是Leu,Gly,Arg,Thr,Ser,或Ala;Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val,或Trp;Xaa在位点29是Gln,Asn,Leu,Pro,Arg,或Val;Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu,或Lys;Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu,或Gln;Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala,或Glu;Xaa在位点33是Pro,Leu,Gln,Ala,Thr,或Glu;Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,
或Met;Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln,或Val;Xaa在位点36是Asp,Leu,或Val;Xaa在位点37是Phe,Ser,Pro,Trp,或Ile;Xaa在位点38是Asn,或Ala;Xaa在位点40是Leu,Trp,或Arg;Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro;Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr
Ile,Met,或Ala;Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,
Gly,或Ser;Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,
Ala,或Pro;Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,
Arg,Ser,Ala,Ile,Glu,或His;Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,
Tyr,Ile,Val,或Gly;Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro,或His;Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,
Val,或Asn;Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His,或Asp;Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,
Phe,Met,或Gln;Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr,或His;Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser,或Thr;Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,或Met;Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或
Leu;Xaa在位点55是Arg,Thr,Val,Ser,Leu,或Gly;Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,
Leu,Val,或Lys;Xaa在位点57是Asn,或Gly;Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val,或Cys;Xaa在位点59是Glu,Tyr,His,Leu,Pro,或Arg;Xaa在位点60是Ala,Ser,Pro,Tyr,Asn,或Thr;Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg,或Ser;Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp,或Ile;Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro,或Val;Xaa在位点64是Ala,Asn,Pro,Ser,或Lys;Xaa在位点65是Val,Thr,Pro,His,Leu,Phe,或Ser;Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu,或Ser;Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro,或His;Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr,或His;Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly,或Leu;Xaa在位点70是Asn,Leu,Val,Trp,Pro,或Ala;Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,或Asn;Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg,或Asp;Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr,或Arg;Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala;Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln或Leu;Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly,或Asp;Xaa在位点77是Ile,Ser,Arg,Thr,或Leu;Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly,或Arg;Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly,或Asp;Xaa在位点80是Asn,Trp,Val,Gly, Thr,Leu,Glu,或Arg;Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val,或Lys;Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,
Ala,Tyr,Phe,Ile,Met,或Val;Xaa在位点83是Pro,Ala,Thr,Trp,Arg,或Met;Xaa在位点84是Cys,Glu,Gly,Arg,Met,或Val;Xaa在位点85是Leu,Asn,Val,或Gln;Xaa在位点86是Pro,Cys,Arg,Ala,或Lys;Xaa在位点87是Leu,Ser,Trp,或Gly;Xaa在位点88是Ala,Lys,Arg,Val,或Trp;Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn,或Ser;Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile,或Met;Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp,或His;Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile,或Leu;Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu,或Arg;Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala,或Pro;Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,
Trp,Phe,Ile,或Tyr;Xaa在位点96是Pro,Lys,Tyr,Gly,Ile,或Thr;Xaa在位点97是Ile,Val,Lys,Ala,或Asn;Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,
Val,Lys,Arg,Tyr,或Pro;Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe,或His;Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,或Pro;Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,
Ala,Gly,Ile,Leu,或Gln;Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr,或Pro;Xaa在位点103是Asp,或Ser;Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,
Phe,或Gly;Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,
Asp,或His;Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly,或Pro;Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala,或Pro;Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser,或Gly;Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,或Trp;Xaa在位点111是Leu,Ile,Arg,Asp,或Met;Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser,或Phe;Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,
或Asn;Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg,或Leu;Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp,或Met;Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,
Asn,His,Ala,Tyr,Phe,Gln,或Ile;Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys,或Pro;Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp,或Tyr;Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr,或Arg;Xaa在位点120是Asn,Ala,Pro,Leu,His,Val,或Gln;Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp,或Gly;Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr,或Cys;Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr,或Leu;
其中任选地可从所说修饰的人IL-3氨基酸序列删除N-末端的1-14氨基酸和/或C-末端的1-15氨基酸;其中被称为Xaa的1-44氨基酸与1-133位天然人白介素-3对应的氨基酸不同;
其中L1是能够将R1连接到R2上的接头;并且所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
7.权利要求4或6的造血蛋白,其中R2选自下组:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala GluAsp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn LeuGlu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln(SEQ ID NO:225);Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser GluAsp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn LeuLeu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln(SEQ ID NO:226);Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysVal Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser GluAsp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn LeuLeu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln(SEQ ID NO:227);和Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln(SEQ ID NO:228)。
8.权利要求1的造血蛋白,其包括有下述通式的氨基酸序列:
R1-L1-R2,R2-L1-R1,R1-R2,或R2-R1
其中R1是一种多肽,包括具有如下通式的修饰的人c-mpl的氨基酸序列:SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer1 5 10 15HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro20 25 30 35ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu40 45 50 55ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
60 65 70 75AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
80 85 90 95GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa
100 105 110XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis115 120 125 130LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal135 140 145 150Arg(SEQ ID NO:256)153其中;Xaa在位点112被删去或者是Leu,Ala,Val,Ile,Pro,Phe,Trp,或Met;Xaa在位点113被删去或者是Pr0,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点114被删去或者是Pro,Phe,Ala,Val,Leu,Ile,Trp,或Met;Xaa在位点115被删去或者是Gln,Gly,Ser,Thr,Tyr,或Asn;和
其中可将N-末端直接或通过一个能将N-末端连接到C-末端上的接头L2连接到C-末端上并在如下氨基酸上分别具有新的N-和C-末端;
26-27 51-52 108-109
27-28 52-53 109-110
28-29 53-54 110-111
29-30 54-55 111-112
30-31 55-56 112-113
32-33 56-57 113-114
33-34 57-58 114-115
34-35 58-59 115-116
36-37 59-60 116-117
37-38 78-79 117-118
38-39 79-80 118-119
40-41 80-81 119-120
41-42 81-82 120-121
42-43 82-83 121-122
43-44 83-84 122-123
44-45 84-85 123-124
46-47 85-86 124-125
47-48 86-87 125-126
48-49 87-88 126-127
50-51 88-89 or 127-128其中R2是G-CSF或G-CSF Ser17;
其中L1是能够将R1连接到R2上的接头;并且所说造血蛋白可任选地直接以Met-1、Ala-1或Met-2Ala-1起始。
9.权利要求1,2,3,4,5,6或8的造血蛋白,其中所说接头L2选自下组:GlyGlyGlySer(SEQ ID NO:12);GlyGlyGlySerGlyGlyGlySer(SEQ ID NO:242);GlyGlyGlySerGlyGlyGlySerGlyGlyGlySer(SEQ ID NO:243);SerGlyGlySerGlyGlySer(SEQ ID NO:244);GluPheGlyAsnMetAla(SEQ ID NO:245);GluPheGlyGlyAsnMetAla(SEQ ID NO:246);GluPheGlyGlyAsnGlyGlyAsnMetAla(SEQ ID NO:247);andGlyGlySerAspMetAlaGly(SEQ ID NO:248)。
10.权利要求7的造血蛋白,其中接头L2选自下组:GlyGlyGlySer(SEQ ID NO:12);GlyGlyGlySerGlyGlyGlySer(SEQ ID NO:242);GlyGlyGlySerGlyGlyGlySerGlyGlyGlySer(SEQ ID NO:243);SerGlyGlySerGlyGlySer(SEQ ID NO:244);GluPheGlyAsnMetAla(SEQ ID NO:245);GluPheGlyGlyAsnMetAla(SEQ ID NO:246);GluPheGlyGlyAsnGlyGlyAsnMetAla(SEQ ID NO:247);andGlyGlySerAspMetAlaGly(SEQ ID NO:248)。
11.权利要求1的造血蛋白,其中所说蛋白选自下组:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr(SEQ ID NO:166);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr(SEQ ID NO:167);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser(SEQ ID NO:168);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser(SEQ ID NO:169);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProSer Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SarCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln LeuHis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu GluGly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln LeuAsp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu GluLeu Gly(SEQ ID NO:170);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProSer Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln LeuHis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu GluGly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln LeuAsp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu GluLeu Gly(SEQ ID NO:171);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly SerGln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile GlnGly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu GlnLeu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu TyrGln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro(SEQ ID NO:172);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly SerGln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile GlnGly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu GlnLeu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu TyrGln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro(SEQ ID NO:173);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu AspVal Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro AlaPhe Ala (SEQ ID NO:177);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro SerGly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu GluGln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser CysPro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu HisSer Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu GlyIle Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu AspVal Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro AlaPhe Ala(SEQ ID NO:175);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr(SEQ ID NO:176);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu CysHis Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile ProTrp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu AlaGly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln GlyLeu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro ThrLeu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr IleTrp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro LeuGly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser LeuGlu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln GluLys Leu Cys Ala Thr(SEQ ID NO:177);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu GlyPro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala ThrThr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala LeuGln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser(SEQ ID NO:179);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro AlaLeu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala PheGln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln SerPhe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln ProThr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu LeuLys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala AlaLeu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro GluGlu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala ProLeu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys LeuSer Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln GlnMet Glu Glu Leu Gly(SEQ ID NO:181);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val ArgLys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys AlaThr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly HisSer Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser GlnAla Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser ProGlu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala AspPhe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met AlaPro Ala Leu Gln Pro(SEQ ID NO:182);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Glu Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly AlaMet Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly ValLeu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val ArgLys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys AlaThr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly HisSer Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser GlnAla Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser ProGlu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala AspPhe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met AlaPro Ala Leu Gln Pro(SEQ ID NO:183);Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly IleGlu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala ThrAla Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe GlnArg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro ThrPro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu LysSer Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala LeuGln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu GluLeu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro LeuSer Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr LeuGln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln MetGlu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly AlaMet Pro Ala Phe Ala(SEQ ID NO:184);MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrgGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThr(SEQ ID NO:194);MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer(SEQ ID NO:195);MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAla(SEQ ID NO:196);MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGly(SEQ ID NO:197);MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:198);Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp GluAsp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn LeuGlu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Gly Pro Thr Cys LeuSer Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu LeuGly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln GlyArg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser PheGln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val GlyGly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala SerPro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu LeuArg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro GluVal His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp PheSer Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala GlnAsp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met AlaAla Arg Gly Gln Leu(SEQ ID NO:209);Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp GluAsp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn LeuGlu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Gly Thr Gln Leu ProPro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile PheLeu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu MetLeu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly AsnMet Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu SerLys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser GlnCys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro AlaVal Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu ThrLys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu GlyVal Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser SerLeu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly AlaLeu Gln Ser Leu Leu(SEQ ID NO:210);Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp GluAsp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn LeuGlu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Gly Arg Thr Thr AlaHis Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu LeuArg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr LeuCys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro ProAla Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser HisVal Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro LeuPro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly GluTrp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu GlyAla Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly GlnLeu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser GlyGln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly ThrGln Leu Pro Pro Gln(SEQ ID NO:211);Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp GluAsp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn LeuGlu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser GlyIle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser AlaThr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser ProGly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro ProSer Lys Glu Ser His Lys Ser Pro Asn Met Ala His Lys Asp ProAsn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys ValArg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg GluPhe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp LeuArg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His SerArg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro ValLeu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr GlnMet Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr LeuLeu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro ThrCys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg LeuLeu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro ProGln Gly Arg Thr Thr(SEQ ID NO:212);Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg AlaVal Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu ArgAsn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser ArgHis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg GluLys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile IleHis His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:186);Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile IleLys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe TyrLeu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly SerAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys ArgPro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu AspVal Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu GluSer Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:187);Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu LeuAsp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met AspArg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala ValLys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg AsnLeu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly GlyGly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met AlaThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu GluVal Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly GlySer Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu CysAla Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu GlyHis Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro SerGln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser GlyLeu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val AlaAsp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly MetAla Pro Ala Leu Gln Pro(SEQ ID NO:189);Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg AlaVal Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu ArgAsn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser ArgHis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg GluLys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn CysSer Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro ProAla Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro(SEQID NO:190);Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile IleLys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe TyrLeu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly SerGly Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu AspPro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp ArgAsn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val LysAsn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu ProSer Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro AlaPhe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val AlaSer His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu ArgHis Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro;(SEQ ID NO:191)MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleHisIlelysAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro;(SEQ ID NO:199)MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:200);MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro;(SEQ ID NO:201)MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro(SEQ ID NO:202);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHislysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu(SEQ ID NO:221);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsuAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu(SEQ ID NO:222);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu(SEQ ID NO:223;AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyVaLMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu(SEQ ID NO:234);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln(SEQ ID NO:235);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr(SEQ ID NO:236);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys(SEQ ID NO:237);AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsn(SEQ ID NO:238);andAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLys(SEQ ID NO:239)
12.权利要求1,2,3,4,5,6,8或9的造血蛋白,其中所说集落刺激因子选自:GM-CSF,G-CSF,G-CSF Ser17,c-mpl配体TPO,M-CSF,红细胞生成素EPO,IL-1,IL-4,IL-2,IL-3,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-1 1,IL-12,IL-13,IL-15,LIF,flt3/flk2配体,人生长激素,B细胞生长因子,B细胞分化因子,嗜酸性粒细胞分化因子,和干细胞因子SCF。
13.权利要求12的造血蛋白,其中所说集落刺激因子选自G-CSF,G-CSF SerI7和c-mpl配体TPO。
14.编码权利要求1的造血蛋白的核酸分子。
15.编码权利要求2的造血蛋白的核酸分子。
16.编码权利要求3的造血蛋白的核酸分子。
17.编码权利要求4的造血蛋白的核酸分子。
18.编码权利要求5的造血蛋白的核酸分子。
19.编码权利要求6的造血蛋白的核酸分子。
20.编码权利要求7的造血蛋白的核酸分子。
21.编码权利要求8的造血蛋白的核酸分子。
22.编码权利要求9的造血蛋白的核酸分子。
23.编码权利要求10的造血蛋白的核酸分子。
24.编码权利要求11的造血蛋白的核酸分子。
25.编码权利要求12的造血蛋白的核酸分子。
26.编码权利要求13的造血蛋白的核酸分子。
27.权利要求23的核酸分子,其选自下组:1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC801 GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG CTCAAGTCTT851 TAGAGCAAGT GAGAA GATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG901 CTGTGTGCCA CCTAATAA(SEQ ID NO:94);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC851 CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG901 CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG951 TGCCACCTAA TAA(SEQ ID NO:95); 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC401 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT451 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT501 GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC551 GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG601 TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG651 CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG701 GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC751 CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC801 TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA851 GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG901 GAAGGGATAT CCTAATAA(SEQ ID NO:96);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA651 CCGCGTTCTA CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC701 AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT751 GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC801 CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC851 TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA901 CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG951 GATATCCTAA TAA(SEQ ID NO:97);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT451 GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG501 CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCTCTG551 GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG601 AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC651 CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG701 GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG751 GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT801 CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA851 CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG901 GAAGAACTGG GATAATAA(SEQ ID NO:98);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC601 TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA651 GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA701 AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC751 CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG801 CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC851 AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG901 CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA951 ACTGGGATAA TAA(SEQ ID NO:99);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA451 GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG501 CGTTCTACGC CACCTTGCGC AGCCCTCTGG CGGCTCTGGC GGCTCTCAGA551 GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GGGCGATGGC601 GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA651 GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA701 GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC751 CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT801 ATCCCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG851 ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT901 GCCCTGCAGC CCTAATAA(SEQ ID NO:100);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT951 GCAGCCCTAA TAA(SEQ ID NO:101);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG451 AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTC501 TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG551 TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC601 ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT651 GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC701 TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG751 CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA801 CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA851 TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG901 CCGGCCTTCG CCTAATAA(SEQ ID NO:102);pMON251911 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA651 CCGCGTTCTA CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT701 CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT TAGAGCAAGT GAGAAAGATC751 CAGGGCGATG GCGCAGCGCT CCAGGAGAAG CTGTGTGCCA CCTACAAGCT801 GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG GGCATCCCCT851 GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC901 TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC951 CCTGGAAGGG ATATCCTAAT AA(SEQ ID NO:107);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTCTGCT451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG551 GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA601 AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA651 CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA701 TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA751 GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT801 GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC851 TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA901 GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC951 CTTCGCCTAA TAA(SEQ ID NO:103);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC801 GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC851 TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC901 CAGGAGAAGC TGTGTGCCAC CTAATAA(SEQ ID NO:104);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC851 CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG901 TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA951 GAAGCTGTGT GCCACCTAAT AA(SEQ ID NO:105);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CACACCATTG601 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA651 AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA951 GATGGAAGAA CTGGGATAAT AA(SEQ ID NO:109); 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA401 CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA451 GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG501 CGTTCTACGC CACCTTGCGC AGCCCACACC ATTGGGCCCT GCCAGCTCCC551 TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AAAGATCCAG601 GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG651 CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG701 CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG751 AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT801 GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG851 ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA901 ATGGCCCCTG CCCTGCAGCC CTAATAA(SEQ ID NO:110);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC951 CCCTGCCCTG CAGCCCTAAT AA(SEQ ID NO:111);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT401 CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG451 AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCAC501 ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT551 TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG601 CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG651 ACACTCTCTG GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG701 CCCTGCAGCT GGCAGGCTGC TTGAGCCAAC TCCATAGCGG CCTTTTCCTC751 TACCAGGGGC TCCTGCAGGC CCTGGAAGGG ATATCCCCCG AGTTGGGTCC801 CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC ACCACCATCT851 GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG901 GGTGCCATGC CGGCCTTCGC CTAATAA(SEQ ID NO:112);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTACAAG451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC851 CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG901 CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG951 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA(SEQ IDNO:155);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTCCCGAG451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA651 CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA701 CACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT751 TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA801 GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG851 GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG901 GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT951 CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCTAA TAA(SEQ IDNO:156);1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTCTGCT451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCGGCGGCG551 GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC601 TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC651 AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG701 AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC751 TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA801 TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT851 CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC901 TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC951 CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTAA TAA;(SEQID NO:157)1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTATGGCC451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CGGCGGCGGC601 TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT651 CCTGCTCAAG TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG701 CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CCCCGAGGAG751 CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC801 CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA851 GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AGGGATATCC901 CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT951 TGCCACCACC ATCTGGCAGC AGATGGAAGA ACTGGGATAA TAA;(SEQID NO:158) 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TACACCATTA601 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA651 AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA951 GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA;(SEQID NO:159)GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG(SEQ ID NO:124);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT(SEQ ID NO:125);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG(SEQ ID NO:126);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA(SEQ ID NO:127);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:128);1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC251 CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT951 GCAGCCCTAA TAA(SEQ ID NO:114);1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATCTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC251 CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG851 GGATATCCGC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC951 CCCTGCCCTG CAGCCCTAAT AA(SEQ ID NO:115);1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC251 CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT951 GCAGCCCTAA TAA(SEQ ID NO:116);1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG101 ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA201 AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC251 CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC951 CCCTGCCCTG CAGCCCTAAT AA(SEQ ID NO:117);1 ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT51 GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA101 AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA151 CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT201 CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG251 TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT301 ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT351 GTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:86);1 ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG51 TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG101 CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC151 CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTAACT GCTCTATAAT201 GATCCATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA CCTTTGCTGG251 ACCCGAAAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC301 CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA351 ATACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:87);1 ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA51 AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC101 AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CGATGAAATT151 ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT201 CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA251 ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT301 ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC351 CTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGG CAG GCTGCTTGAG801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT951 GGCCCCTGCC CTGCAGCCCT AATAA(SEQ ID NO:88);1 ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT51 GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA101 AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA151 CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT201 CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG251 TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TGGCGGTGGC301 AGCGGCGGCG GTTCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA351 CTTAAAGAGA CCACCTGCAC CTTTGTACGT AGAGGGCGGT GGAGGCTCCC401 CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC501 CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC551 ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG601 CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT651 AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC701 TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA751 CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC801 CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT851 ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC901 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA(SEQ ID NO:90);1 ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG51 TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG101 CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC151 CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTGGCG GTGGCAGCGG201 CGGCGGTTCT AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA251 AGAGACCACC TGCACCTTTG CTGGACCCGA ACAACCTCAA TGACGAAGAC301 GTCTCTATCC TGATGGACCG AAACCTTCGA CTTCCAAACC TGGAGAGCTT351 CGTAAGGGCT GTCAAGAACT TAGAATACGT AGAGGGCGGT GGAGGCTCCC401 CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC501 CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC551 ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG601 CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT651 AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC701 TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA751 CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC801 CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT851 ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC901 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA(SEQ ID NO:91);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG(SEQ ID NO:136);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT(SEQ ID NO:137);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG(SEQ ID NO:148);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT(SEQ ID NO:149);GCTAACTGCTCTATAATGATCGAT AAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG(SEQ ID NO:150);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA(SEQ ID NO:151);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:152);GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT(SEQ ID NO:153);andGCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGTCCACC CTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCGTCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAG(SEQ ID NO:154)
28.一种制备造血蛋白的方法,其包括:在适当的营养条件下,以允许所说造血蛋白表达的方式培养用可复制载体转化或转染的宿主细胞并回收所说造血蛋白,其中可复制载体包含权利要求14,15,16,17,18,19,20,21,22,23,24,25,26或27的核酸分子。
29.一种药物组合物,其包含权利要求1,2,3,4,5,6,8,9,10,11或12的造血蛋白和药学上可接受的载体。
30.权利要求1-12中任一权项的造血蛋白在制备在患者中刺激造血细胞产生的药物中的用途。
31.一种选择性地体外扩增干细胞的方法,包括如下步骤:
(a)从其他细胞中分离出干细胞;
(b)用包含权利要求1-12中任一权项的造血蛋白的选定的培养基培养所分离的干细胞;并
(c)收获所培养的细胞。
32.权利要求1-12中任一权项的造血蛋白在制备用于治疗造血紊乱患者的培养基中的用途。
33.权利要求1-12中任一权项的造血蛋白在制备用于人基因治疗的培养基中的用途。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US483495P | 1995-10-05 | 1995-10-05 | |
US60/004,834 | 1995-10-05 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA031551432A Division CN1590407A (zh) | 1995-10-05 | 1996-10-04 | 多功能性造血受体激动剂 |
Publications (2)
Publication Number | Publication Date |
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CN1204369A CN1204369A (zh) | 1999-01-06 |
CN1124348C true CN1124348C (zh) | 2003-10-15 |
Family
ID=21712756
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA031551432A Pending CN1590407A (zh) | 1995-10-05 | 1996-10-04 | 多功能性造血受体激动剂 |
CN96198815A Expired - Fee Related CN1124348C (zh) | 1995-10-05 | 1996-10-04 | 多功能性造血受体激动剂 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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CNA031551432A Pending CN1590407A (zh) | 1995-10-05 | 1996-10-04 | 多功能性造血受体激动剂 |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP0854928A2 (zh) |
JP (1) | JPH11510062A (zh) |
KR (1) | KR100456212B1 (zh) |
CN (2) | CN1590407A (zh) |
AU (1) | AU705083B2 (zh) |
BR (1) | BRPI9610977A2 (zh) |
CA (1) | CA2234061A1 (zh) |
CZ (1) | CZ295518B6 (zh) |
IL (1) | IL123832A0 (zh) |
MX (1) | MX9802730A (zh) |
NO (1) | NO981500L (zh) |
NZ (1) | NZ320978A (zh) |
PL (1) | PL184424B1 (zh) |
WO (1) | WO1997012985A2 (zh) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5581476A (en) | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
US6967092B1 (en) | 1996-10-25 | 2005-11-22 | Mc Kearn John P | Multi-functional chimeric hematopoietic receptor agonists |
US6660257B1 (en) * | 1996-10-25 | 2003-12-09 | Pharmacia Corporation | Circular permuteins of flt3 ligand |
US5969105A (en) * | 1996-10-25 | 1999-10-19 | Feng; Yiqing | Stem cell factor receptor agonists |
US6187564B1 (en) | 1997-07-10 | 2001-02-13 | Beth Israel Deaconess Medical Center | DNA encoding erythropoietin multimers having modified 5′ and 3′ sequences and its use to prepare EPO therapeutics |
US6242570B1 (en) | 1997-07-10 | 2001-06-05 | Beth Israel Deaconess Medical Center | Production and use of recombinant protein multimers with increased biological activity |
US6165476A (en) * | 1997-07-10 | 2000-12-26 | Beth Israel Deaconess Medical Center | Fusion proteins with an immunoglobulin hinge region linker |
AU7825500A (en) * | 1999-10-07 | 2001-04-23 | Pharmacia Corporation | Inhibition enzyme linked immunosorbent assay (iELISA) for the detection and quantification of antibodies in biological samples |
EP1425304B9 (en) | 2001-07-11 | 2010-09-08 | Maxygen, Inc. | G-csf conjugates |
AU2006254543A1 (en) | 2005-06-01 | 2006-12-07 | Maxygen Holdings Ltd. | PEGylated G-CSF polypeptides and methods of producing same |
WO2007075899A2 (en) * | 2005-12-21 | 2007-07-05 | Maxygen, Inc. | Dual agonist compounds and uses thereof |
CN102675472B (zh) * | 2012-05-07 | 2014-07-30 | 北京诺派生物科技有限公司 | 用于检测猪繁殖与呼吸综合症患猪的试剂盒 |
US10426799B2 (en) | 2012-12-21 | 2019-10-01 | Astellas Institute For Regenerative Medicine | Methods for production of platelets from pluripotent stem cells and compositions thereof |
LT6161B (lt) | 2013-09-27 | 2015-06-25 | Uab Profarma | Granuliocitų kolonijas stimuliuojančio faktoriaus sulieti baltymai su kitais augimo faktoriais, optimaliai su kamieninių ląstelių faktoriumi, ir jų gavimo būdas |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU5355790A (en) * | 1989-04-19 | 1990-11-16 | Cetus Corporation | Multifunctional m-csf proteins and genes encoding therefor |
US5738849A (en) * | 1992-11-24 | 1998-04-14 | G. D. Searle & Co. | Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them |
US6057133A (en) * | 1992-11-24 | 2000-05-02 | G. D. Searle | Multivariant human IL-3 fusion proteins and their recombinant production |
US5635599A (en) * | 1994-04-08 | 1997-06-03 | The United States Of America As Represented By The Department Of Health And Human Services | Fusion proteins comprising circularly permuted ligands |
-
1996
- 1996-10-04 CZ CZ1998965A patent/CZ295518B6/cs not_active IP Right Cessation
- 1996-10-04 EP EP96936114A patent/EP0854928A2/en not_active Withdrawn
- 1996-10-04 CN CNA031551432A patent/CN1590407A/zh active Pending
- 1996-10-04 NZ NZ320978A patent/NZ320978A/en unknown
- 1996-10-04 IL IL12383296A patent/IL123832A0/xx unknown
- 1996-10-04 KR KR10-1998-0702547A patent/KR100456212B1/ko not_active IP Right Cessation
- 1996-10-04 WO PCT/US1996/015774 patent/WO1997012985A2/en not_active Application Discontinuation
- 1996-10-04 JP JP9514385A patent/JPH11510062A/ja not_active Abandoned
- 1996-10-04 BR BRPI9610977A patent/BRPI9610977A2/pt not_active IP Right Cessation
- 1996-10-04 CN CN96198815A patent/CN1124348C/zh not_active Expired - Fee Related
- 1996-10-04 CA CA002234061A patent/CA2234061A1/en not_active Abandoned
- 1996-10-04 PL PL96326072A patent/PL184424B1/pl not_active IP Right Cessation
- 1996-10-04 AU AU73844/96A patent/AU705083B2/en not_active Ceased
-
1998
- 1998-04-02 NO NO981500A patent/NO981500L/no not_active Application Discontinuation
- 1998-04-06 MX MX9802730A patent/MX9802730A/es not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
KR19990064068A (ko) | 1999-07-26 |
CZ295518B6 (cs) | 2005-08-17 |
KR100456212B1 (ko) | 2005-01-15 |
EP0854928A2 (en) | 1998-07-29 |
NO981500D0 (no) | 1998-04-02 |
JPH11510062A (ja) | 1999-09-07 |
CA2234061A1 (en) | 1997-04-10 |
PL184424B1 (pl) | 2002-10-31 |
NZ320978A (en) | 2001-03-30 |
AU705083B2 (en) | 1999-05-13 |
WO1997012985A2 (en) | 1997-04-10 |
NO981500L (no) | 1998-05-20 |
AU7384496A (en) | 1997-04-28 |
IL123832A0 (en) | 1998-10-30 |
CN1590407A (zh) | 2005-03-09 |
CN1204369A (zh) | 1999-01-06 |
PL326072A1 (en) | 1998-08-17 |
CZ96598A3 (cs) | 1998-09-16 |
MX9802730A (es) | 1998-09-30 |
BRPI9610977A2 (pt) | 2019-09-17 |
WO1997012985A3 (en) | 1997-08-07 |
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